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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Faz-se uma revis&#227;o da interven&#231;&#227;o da c&#233;lula epitelial br&#244;nquica na fisiopatologia da asma&#46; O epit&#233;lio que reveste as vias respirat&#243;rias actua como uma barreira f&#237;sica&#44; separando o meio externo do meio interno pulmonar&#44; controla a permeabilidade intercelular e transcelular&#44; e&#44; deste modo&#44; a acessibilidade dos agressores inalantes &#224;s c&#233;lulas apresentadoras de antig&#233;nio envolvidas na resposta imunoinflamat&#243;ria&#46; As c&#233;lulas epiteliais unidas por <span class="elsevierStyleItalic">tight junctions</span> contribuem para a integridade das vias a&#233;reas e expressam <span class="elsevierStyleItalic">poliovirus receptor&#8211; related protein</span> &#40;PRR&#41;&#44; toll like receptors &#40;TLR&#41; e <span class="elsevierStyleItalic">protease-activated receptors</span> &#40;PAR&#41;&#44; que reconhecem agentes bacterianos e alerg&#233;nios&#46; A sua disfun&#231;&#227;o transforma-as em fonte de mediadores intervenientes na inflama&#231;&#227;o&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A interac&#231;&#227;o bidireccional entre&#44; por um lado&#44; o epit&#233;lio e os elementos constitutivos do br&#244;nquio e por outro&#44; as part&#237;culas inaladas&#44; tem subjacente a forma&#231;&#227;o de uma unidade&#44; com identidade pr&#243;pria designada EMTU &#8211; <span class="elsevierStyleItalic">epithelial mesenchymal trophic unit</span>&#46;</p><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Esta extensa interven&#231;&#227;o coloca a c&#233;lula epitelial no centro de ac&#231;&#227;o da cronicidade e remodela&#231;&#227;o do processo asm&#225;tico&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">As doen&#231;as infecciosas e o <span class="elsevierStyleItalic">stress</span> ambiental s&#227;o capazes de induzir altera&#231;&#245;es a n&#237;vel da c&#233;lula epitelial suscept&#237;veis de modificar a sua resposta a estimula&#231;&#245;es futuras&#44; nomeadamente a ampliar a resposta a outras agress&#245;es infecciosas por ac&#231;&#227;o sin&#233;rgica das vias de sinaliza&#231;&#227;o&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">O epit&#233;lio br&#244;nquico tem assim fun&#231;&#245;es de barreira que lhe permite exercer uma permeabilidade selectiva&#44; a n&#237;vel intracelular e transcelular&#44; &#233; ainda metabolicamente activo pelas capacidade de produzir mediadores quimiot&#225;cticos e citocinas envolvidos no recrutamento e na activa&#231;&#227;o celular&#44; com repercuss&#227;o na broncomotricidade e na remodela&#231;&#227;o da parede br&#244;nquica&#46;</p>"
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        "resumen" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">It is done a review of the intervention of the epithelial bronchial cell in the pathophysiology of asthma&#46; The respiratory epithelium acts as a physical barrier that separates the external environment from the pulmonary internal environment&#46; It controls the intercellular and trans-cellular permeability and this way the accessibility of the inhaled pathogens to the antigen presenting cells involved in the immuno-inflammatory response&#46; Epithelial cells connected by tight junctions contribute to the barrier function of the airways&#46; They express a poliovirus receiver &#8211; related protein &#40;PRR&#41;&#44; toll like receptors &#40;TLRs&#41; and protease-activated receptors &#40;PARs&#41;&#44; which recognize bacterial agents and allergens&#46; Its dysfunction turns them into important sources of inflammatory mediators&#46;</p><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The bidirectional interaction between the epithelium and other bronchial wall elements with inhaled particles originates a structure with its own identity&#44; the designated EMTU &#8211; Epithelial Mesenchymal Trophic Unit&#46;</p><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">These observations support a central role for the epithelial cell in chronic inflammation and in the remodelling of the asthmatic process&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Infectious diseases and environmental stress can activate different cell receptors and signalling pathways that induce changes in the cell surface modifying their response to future stimulations&#44; namely to other infectious aggressions&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The bronchial epithelium has barrier functions with selective permeability&#59; it has metabolic activity producing cytokines and chemokines stimulating the cell&#39;s recruitment and activation&#44; increasing the bronchial reactivity and the remodelling of the airways&#46;</p>"
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                    0 => array:2 [
                      "doi" => "10.1111/j.1398-9995.2008.01785.x"
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                        "tituloSerie" => "Allergy"
                        "fecha" => "2008"
                        "volumen" => "63"
                        "numero" => "9"
                        "paginaInicial" => "1110"
                        "paginaFinal" => "1123"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18699929"
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                    0 => array:2 [
                      "titulo" => "Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Renato Colognato"
                            1 => "J&#46;R&#46; Slupsky"
                            2 => "M&#46; Jendrach"
                            3 => "L&#46; Burysek"
                            4 => "T&#46; Syrovets"
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                          ]
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                    0 => array:2 [
                      "doi" => "10.1182/blood-2002-08-2497"
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                        "tituloSerie" => "Blood"
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                        "volumen" => "102"
                        "paginaInicial" => "2645"
                        "paginaFinal" => "2652"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12805069"
                            "web" => "Medline"
                          ]
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                ]
              ]
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                    0 => array:2 [
                      "titulo" => "Dendritic cells and epithelial cells&#58; linking innate and adaptive immunity in asthma"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "Hammad Hamida"
                            1 => "B&#46;N&#46; Lambrecht"
                          ]
                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Nature Rev"
                        "fecha" => "2008"
                        "volumen" => "8"
                        "paginaInicial" => "193"
                        "paginaFinal" => "204"
                      ]
                    ]
                  ]
                ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pen ch 13 allergen induces secretion of mediators and degradation of occludin protein of human lung epithelial cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [
                            0 => "H&#46;Y&#46; Tai"
                            1 => "M&#46;F&#46; Tam"
                            2 => "H&#46; Chou"
                            3 => "H&#46;J&#46; Peng"
                            4 => "S&#46;N&#46; Su"
                            5 => "D&#46;W&#46; Perng"
                            6 => "H&#46;D&#46; Shen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1398-9995.2005.00958.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy"
                        "fecha" => "2006"
                        "volumen" => "61"
                        "paginaInicial" => "382"
                        "paginaFinal" => "388"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16436150"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib13"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Purification of a novel aminopeptidase from the pollen of pariet&#225;ria-judaica that alters epithelial integrity and degrades neuropeptides"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Cortes"
                            1 => "A&#46;L&#46; Carvalho"
                            2 => "A&#46; Todo-Bom"
                            3 => "C&#46; Faro"
                            4 => "E&#46; Pires"
                            5 => "P&#46; Ver&#237;ssimo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2006.05.029"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2006"
                        "volumen" => "118"
                        "numero" => "4"
                        "paginaInicial" => "878"
                        "paginaFinal" => "884"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17030241"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib14"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathogen recognition with Toll-like receptors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Kawai Taro"
                            1 => "S&#46; Akira"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.coi.2005.02.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Immunol"
                        "fecha" => "2005"
                        "volumen" => "17"
                        "paginaInicial" => "338"
                        "paginaFinal" => "344"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15950447"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib15"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "No Bit PARt for PAR-1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Laurent Geoffrey"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/rcmb.F304"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2005"
                        "volumen" => "33"
                        "paginaInicial" => "213"
                        "paginaFinal" => "215"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16107573"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Proteinase-activated receptor-1 mediates elastase-induced apoptosis of human lung epithelial cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Tomoko Suzuki"
                            1 => "T&#46;J&#46; Moraes"
                            2 => "E&#46; Vachon"
                            3 => "H&#46;H&#46; Ginzberg"
                            4 => "T&#46;T&#46; Huang"
                            5 => "M&#46;A&#46; Matthay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/rcmb.2005-0109OC"
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                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2005"
                        "volumen" => "33"
                        "paginaInicial" => "231"
                        "paginaFinal" => "247"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15891109"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Proteinase-activated receptor-2 promotes allergic sensitization to an inhaled antigen through a TNF-mediated pathway"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Cory Ebeling"
                            1 => "T&#46; Lam"
                            2 => "J&#46;R&#46; Gordon"
                            3 => "M&#46;D&#46; Hollenberg"
                            4 => "H&#46; Vliagoftis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2007"
                        "volumen" => "179"
                        "paginaInicial" => "2910"
                        "paginaFinal" => "2917"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17709505"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib18"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidant and antioxidant balance in the airways and airway diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Rahman Irfan"
                            1 => "S&#46;K&#46; Biswas"
                            2 => "A&#46; Kode"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejphar.2005.12.087"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Pharmacol"
                        "fecha" => "2006"
                        "volumen" => "533"
                        "paginaInicial" => "222"
                        "paginaFinal" => "239"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16500642"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            18 => array:3 [
              "identificador" => "bib19"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Extracellular glutathione peroxidase induction in asthmatic lungs&#58; evidence for redox regulation of expression in human airway epithelial cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Comhair Susy"
                            1 => "P&#46;R&#46; Bhathena"
                            2 => "C&#46; Farver"
                            3 => "F&#46;B&#46; Thunnissen"
                            4 => "S&#46;C&#46; Erzurum"
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                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
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                      "Revista" => array:6 [
                        "tituloSerie" => "FASEB J"
                        "fecha" => "2001"
                        "volumen" => "15"
                        "paginaInicial" => "70"
                        "paginaFinal" => "78"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11149894"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib20"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TH2 polarization by Der p 1&#8211; pulsed monocyte-derived dendritic cells is due to the allergic status of the donors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:5 [
                            0 => "Hamida Hammad"
                            1 => "A&#46;S&#46; Charbonnier"
                            2 => "C&#46; Duez"
                            3 => "G&#46;A&#46; Jacquet Astewart"
                            4 => "A&#46;B&#46; Tonnel"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2001"
                        "volumen" => "98"
                        "paginaInicial" => "1135"
                        "paginaFinal" => "1141"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11493462"
                            "web" => "Medline"
                          ]
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                      ]
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                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib21"
              "etiqueta" => "21&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The epithelium takes centre stage in asthma and atopic dermatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Holgate Stephen"
                          ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
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                        "tituloSerie" => "Trends Immunol"
                        "fecha" => "2007"
                        "volumen" => "28"
                        "paginaInicial" => "248"
                        "paginaFinal" => "251"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17466594"
                            "web" => "Medline"
                          ]
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              ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Novel functions of two chemokines in allergic disease thymus and activation-regulated chemokine &#40;TARC&#41;&#47;CCL17 and macrophage-derived chemokine &#40;MDC&#41;&#47;CCL22"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Masafumi Arima"
                            1 => "T&#46; Fukuda"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Allergy Clin Immunol Int &#8211; J World Allergy Org"
                        "fecha" => "2006"
                        "volumen" => "18"
                        "numero" => "2"
                        "paginaInicial" => "58"
                        "paginaFinal" => "64"
                        "itemHostRev" => array:3 [
                          "pii" => "S1521694202902536"
                          "estado" => "S300"
                          "issn" => "15216942"
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                ]
              ]
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              "identificador" => "bib23"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity"
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                        0 => array:2 [
                          "etal" => true
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                            1 => "B&#46; O&#8217;Connor"
                            2 => "J&#46; Ratoff"
                            3 => "Q&#46; Meng"
                            4 => "K&#46; Mallett"
                            5 => "D&#46; Cousins"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2005"
                        "volumen" => "174"
                        "paginaInicial" => "8183"
                        "paginaFinal" => "8190"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15944327"
                            "web" => "Medline"
                          ]
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                ]
              ]
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              "identificador" => "bib24"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Substance P in long-lasting asthma&#58; Immunoinflammatory pathways"
                      "autores" => array:1 [
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                          "etal" => false
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                            0 => "Ana Todo-Bom"
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                            2 => "S&#46; Vale Pereira"
                            3 => "V&#46; Alves"
                            4 => "M&#46; Dourado"
                            5 => "M&#46; Santos Rosa"
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                  "host" => array:1 [
                    0 => array:1 [
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                        "tituloSerie" => "Allergy Clin Immunol Int &#8211; J World Allergy Org"
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                        "numero" => "6"
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                        "paginaFinal" => "248"
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                    0 => array:2 [
                      "titulo" => "Inflammatory cells as source of tachykinin-induced mucus secretion in chronic bronchitis"
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                          "etal" => false
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                            0 => "Jochen Springer"
                            1 => "D&#46;A&#46; Groneberg"
                            2 => "R&#46; Pregla"
                            3 => "A&#46; Fischer"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Epithelial-mesenchymal interactions in the pathogenesis of asthma"
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                            0 => "T&#46; Holgate Stephen"
                            1 => "D&#46;E&#46; Davies"
                            2 => "P&#46;M&#46; Lackie"
                            3 => "S&#46;J&#46; Wilson"
                            4 => "S&#46;M&#46; Puddicombe"
                            5 => "J&#46;L&#46; Lordan"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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                        "paginaFinal" => "204"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10669837"
                            "web" => "Medline"
                          ]
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                ]
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                    0 => array:2 [
                      "titulo" => "The role of epithelial injury and repair in the origins of asthma"
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                          "etal" => false
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                            0 => "Tillie-Louise Hackett"
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                  "host" => array:1 [
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                        "tituloSerie" => "Curr Opin Allergy Clin Immunol"
                        "fecha" => "2007"
                        "volumen" => "7"
                        "paginaInicial" => "63"
                        "paginaFinal" => "68"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17218813"
                            "web" => "Medline"
                          ]
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                ]
              ]
            ]
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              "identificador" => "bib28"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Processes involved in the repair of injured airway epithelia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Y&#46; Tesfaigzi"
                          ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Arch Immunol Ther Exp &#40;Warsz&#41;"
                        "fecha" => "2003"
                        "volumen" => "51"
                        "paginaInicial" => "283"
                        "paginaFinal" => "288"
                      ]
                    ]
                  ]
                ]
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            28 => array:3 [
              "identificador" => "bib29"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes&#44; trauma&#44; or inflammation and potently activates mast cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Zoulfia Allakhverdi"
                            1 => "M&#46;R&#46; Comeau"
                            2 => "H&#46;K&#46; Jessup"
                            3 => "B&#46;R&#46; Yoon"
                            4 => "A&#46; Brewer"
                            5 => "S&#46; Chartier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1084/jem.20062211"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Exp Med"
                        "fecha" => "2007"
                        "volumen" => "204"
                        "paginaInicial" => "253"
                        "paginaFinal" => "258"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17242164"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib30"
              "etiqueta" => "30&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TSLP&#58; an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Yong-Jun Liu"
                            1 => "V&#46; Soumelis"
                            2 => "N&#46; Watanabe"
                            3 => "T&#46; Ito"
                            4 => "Y&#46;H&#46; Wang"
                            5 => "R&#46;W&#46; Malefyt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1146/annurev.immunol.25.022106.141718"
                      "Revista" => array:6 [
                        "tituloSerie" => "Annu Rev Immunol"
                        "fecha" => "2007"
                        "volumen" => "25"
                        "paginaInicial" => "193"
                        "paginaFinal" => "219"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17129180"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib31"
              "etiqueta" => "31&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TSLP&#58; finally in the limelight"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Leonard Warren"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Nature Immunol"
                        "fecha" => "2002"
                        "volumen" => "3"
                        "paginaInicial" => "605"
                        "paginaFinal" => "607"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib32"
              "etiqueta" => "32&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epithelial stress and structural remodelling in childhood asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "I&#46;A&#46; Fedorov"
                            1 => "S&#46;J&#46; Wilson"
                            2 => "D&#46;E&#46; Davies"
                            3 => "S&#46;T&#46; Holgate"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2004.030262"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2005"
                        "volumen" => "60"
                        "paginaInicial" => "389"
                        "paginaFinal" => "394"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15860714"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib33"
              "etiqueta" => "33&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Andrea Zanini"
                            1 => "A&#46; Chetta"
                            2 => "M&#46; Saetta"
                            3 => "S&#46; Baraldo"
                            4 => "R&#46; D&#8217;Ippolito"
                            5 => "A&#46; Castagnaro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2007.04.021"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2007"
                        "volumen" => "120"
                        "paginaInicial" => "329"
                        "paginaFinal" => "333"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17559912"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib34"
              "etiqueta" => "34&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Growth factors secreted by bronchial epithelial cells control myofibroblast proliferation&#58; an <span class="elsevierStyleItalic">in vitro</span> co-culture model of airway remodeling in asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Shaoli Zhang"
                            1 => "H&#46; Smartt"
                            2 => "S&#46;T&#46; Holgate"
                            3 => "W&#46;R&#46; Roche"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Lab Invest"
                        "fecha" => "1999"
                        "volumen" => "79"
                        "paginaInicial" => "395"
                        "paginaFinal" => "405"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10211992"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib35"
              "etiqueta" => "35&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute allergen-induced airway remodeling in atopic asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Simon Phipps"
                            1 => "F&#46; Benyahia"
                            2 => "T&#46;T&#46; Ou"
                            3 => "J&#46; Barkans"
                            4 => "D&#46;S&#46; Robinson"
                            5 => "A&#46;B&#46; Kay"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/rcmb.2004-0193OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2004"
                        "volumen" => "31"
                        "paginaInicial" => "626"
                        "paginaFinal" => "632"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15333330"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib36"
              "etiqueta" => "36&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TGF-beta-induced EMT&#58; mechanisms and implications for fibrotic lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46; Willis Brigham"
                            1 => "Z&#46; Borok"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajplung.00163.2007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Lung Cell Mol Physiol"
                        "fecha" => "2007"
                        "volumen" => "293"
                        "paginaInicial" => "L525"
                        "paginaFinal" => "L534"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17631612"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib37"
              "etiqueta" => "37&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tissue fibrocytes in patients with mild asthma&#58; a possible link to thickness of reticular basement membrane&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Nihlberg Kristian"
                            1 => "K&#46; Larsen"
                            2 => "A&#46; Hultgardh-Nilsson"
                            3 => "A&#46; Malmstrom"
                            4 => "L&#46; Bjermer"
                            5 => "G&#46; Westergren-Thorsson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1465-9921-7-50"
                      "Revista" => array:5 [
                        "tituloSerie" => "Respir Res"
                        "fecha" => "2006"
                        "volumen" => "7"
                        "paginaInicial" => "50"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16571120"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib38"
              "etiqueta" => "38&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characterization of human mucin 5B gene expression in airway epithelium and the genomic clone of the amino-terminal and 5-flanking region"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Yin Chen"
                            1 => "Y&#46;H&#46; Zhao"
                            2 => "Y&#46;P&#46; Di"
                            3 => "R&#46; Wu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/ajrcmb.25.5.4298"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2001"
                        "volumen" => "25"
                        "paginaInicial" => "542"
                        "paginaFinal" => "553"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11713095"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib39"
              "etiqueta" => "39&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A morphometric study of mucins and small airway plugging in cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Pierre-Regis Burgel"
                            1 => "D&#46; Montani"
                            2 => "C&#46; Danel"
                            3 => "D&#46;J&#46; Dusser"
                            4 => "J&#46;A&#46; Nadel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2006.062190"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2007"
                        "volumen" => "62"
                        "paginaInicial" => "153"
                        "paginaFinal" => "161"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16928707"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib40"
              "etiqueta" => "40&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Deshmukh Hitesh"
                            1 => "L&#46;M&#46; Case"
                            2 => "S&#46;C&#46; Wesselkamper"
                            3 => "M&#46;T&#46; Borchers"
                            4 => "L&#46;D&#46; Martin"
                            5 => "H&#46;G&#46; Shertzer"
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200408-1003OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2005"
                        "volumen" => "171"
                        "paginaInicial" => "305"
                        "paginaFinal" => "314"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15531749"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib41"
              "etiqueta" => "41&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cooperative effects of Th2 cytokines and allergen on normal and asthmatic bronchial epithelial cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Lordan James"
                            1 => "F&#46; Bucchieri"
                            2 => "A&#46; Richter"
                            3 => "A&#46; Konstantinidis"
                            4 => "J&#46;W&#46; Holloway"
                            5 => "M&#46; Thornber"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "2002"
                        "volumen" => "169"
                        "paginaInicial" => "407"
                        "paginaFinal" => "414"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12077271"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib42"
              "etiqueta" => "42&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypertonic induction of aquaporin-5&#58; novel role of hypoxia-inducible factor-1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Beiyun Zhou"
                            1 => "D&#46;K&#46; Ann"
                            2 => "X&#46; Li"
                            3 => "K&#46;J&#46; Kim"
                            4 => "H&#46; Lin"
                            5 => "P&#46; Minoo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajpcell.00070.2006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Cell Physiol"
                        "fecha" => "2007"
                        "volumen" => "292"
                        "paginaInicial" => "C1280"
                        "paginaFinal" => "C1290"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17108010"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib43"
              "etiqueta" => "43&#46;"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Shear stress regulates aquaporin-5 and airway epithelial barrier function"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46; Sidhaye Venkataramana"
                            1 => "K&#46;S&#46; Schweitzer"
                            2 => "M&#46;J&#46; Caterina"
                            3 => "L&#46; Shimoda"
                            4 => "L&#46;S&#46; King"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.0712287105"
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                        "tituloSerie" => "PNAS"
                        "fecha" => "2008"
                        "volumen" => "105"
                        "numero" => "9"
                        "paginaInicial" => "3345"
                        "paginaFinal" => "3350"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18305162"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The family of five&#58; TIR domain-containing adaptors in Toll-like receptor signalling"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; O&#8217;Neill Luke"
                            1 => "A&#46;G&#46; Bowie"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nri2079"
                      "Revista" => array:8 [
                        "tituloSerie" => "Nat Rev Immunol"
                        "fecha" => "2007"
                        "volumen" => "7"
                        "numero" => "5"
                        "paginaInicial" => "353"
                        "paginaFinal" => "364"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17457343"
                            "web" => "Medline"
                          ]
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                        "itemHostRev" => array:3 [
                          "pii" => "S1699258X05727339"
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                          "issn" => "1699258X"
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                ]
              ]
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            44 => array:3 [
              "identificador" => "bib45"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "The &#8220;wisdom&#8221; of lung surfactant&#58; balancing host defense and surface tension-reducing functions"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Rae Wright Jo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajplung.00261.2006"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Physiol Lung Cell Mol Physiol"
                        "fecha" => "2006"
                        "volumen" => "291"
                        "numero" => "5"
                        "paginaInicial" => "L847"
                        "paginaFinal" => "L850"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16861381"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib46"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Innate immunity&#58; toll-like receptors and some more&#46; a brief history&#44; basic organization and relevance for the human newborn"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Andre Fleer"
                            1 => "T&#46;G&#46; Krediet"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000102054"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neonatology"
                        "fecha" => "2007"
                        "volumen" => "92"
                        "numero" => "3"
                        "paginaInicial" => "145"
                        "paginaFinal" => "157"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17476116"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib47"
              "etiqueta" => "47&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Role of neuraminidase in lethal synergism between influenza virus and <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; McCullers Jonathan"
                            1 => "K&#46;C&#46; Bartmess"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/368163"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "2003"
                        "volumen" => "187"
                        "paginaInicial" => "1000"
                        "paginaFinal" => "1009"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12660947"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "etiqueta" => "48&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Structural changes in the airways in asthma observations and consequences"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46; Bai Tony"
                            1 => "D&#46;A&#46; Knight"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Sci &#40;Lond&#41;"
                        "fecha" => "2005"
                        "volumen" => "108"
                        "paginaInicial" => "463"
                        "paginaFinal" => "477"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib49"
              "etiqueta" => "49&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Synergistic proinflammatory responses induced by polymicrobial colonization of epithelial surfaces"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Ratner Adam"
                            1 => "E&#46;S&#46; Lysenko"
                            2 => "M&#46;N&#46; Paul"
                            3 => "J&#46;N&#46; Weiser"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Proc Natl Acad Sci &#40;USA&#41;"
                        "fecha" => "2005"
                        "volumen" => "102"
                        "paginaInicial" => "3429"
                        "paginaFinal" => "3434"
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib50"
              "etiqueta" => "50&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Respiratory infections&#46; Do we ever recover&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Goulding"
                            1 => "R&#46; Snelgrove"
                            2 => "J&#46; Saldana"
                            3 => "A&#46; Didierlaurent"
                            4 => "M&#46; Cavanagh"
                            5 => "E&#46; Gwyer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1513/pats.200706-066TH"
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                        "tituloSerie" => "Proc Am Thorac Soc"
                        "fecha" => "2007"
                        "volumen" => "4"
                        "paginaInicial" => "618"
                        "paginaFinal" => "625"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18073393"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
            ]
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                    0 => array:2 [
                      "titulo" => "The evolutionary continuum from lung development to homeostasis and repair"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;S&#46; Torday"
                            1 => "V&#46;K&#46; Rehan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajplung.00379.2006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Lung Cell Mol Physiol"
                        "fecha" => "2007"
                        "volumen" => "292"
                        "paginaInicial" => "L608"
                        "paginaFinal" => "L611"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17085519"
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Vol. 15. Issue 3.
Pages 461-472 (May - June 2009)
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Vol. 15. Issue 3.
Pages 461-472 (May - June 2009)
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A intervenção da célula epitelial na asma
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Anabela Mota Pinto1, Ana Todo-Bom2
1 Professora Associada com Agregação de Fisiopatologia – Faculdade de Medicina da Universidade de Coimbra. Directora do Instituto de Patologia Geral
2 Assistente Hospitalar Graduada em Imunoalergologia nos Hospitais da Universidade de Coimbra. Doutoramento em Medicina Interna – Pneumologia pela Faculdade de Medicina da Universidade de Coimbra
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Resumo

Faz-se uma revisão da intervenção da célula epitelial brônquica na fisiopatologia da asma. O epitélio que reveste as vias respiratórias actua como uma barreira física, separando o meio externo do meio interno pulmonar, controla a permeabilidade intercelular e transcelular, e, deste modo, a acessibilidade dos agressores inalantes às células apresentadoras de antigénio envolvidas na resposta imunoinflamatória. As células epiteliais unidas por tight junctions contribuem para a integridade das vias aéreas e expressam poliovirus receptor– related protein (PRR), toll like receptors (TLR) e protease-activated receptors (PAR), que reconhecem agentes bacterianos e alergénios. A sua disfunção transforma-as em fonte de mediadores intervenientes na inflamação.

A interacção bidireccional entre, por um lado, o epitélio e os elementos constitutivos do brônquio e por outro, as partículas inaladas, tem subjacente a formação de uma unidade, com identidade própria designada EMTU – epithelial mesenchymal trophic unit.

Esta extensa intervenção coloca a célula epitelial no centro de acção da cronicidade e remodelação do processo asmático.

As doenças infecciosas e o stress ambiental são capazes de induzir alterações a nível da célula epitelial susceptíveis de modificar a sua resposta a estimulações futuras, nomeadamente a ampliar a resposta a outras agressões infecciosas por acção sinérgica das vias de sinalização.

O epitélio brônquico tem assim funções de barreira que lhe permite exercer uma permeabilidade selectiva, a nível intracelular e transcelular, é ainda metabolicamente activo pelas capacidade de produzir mediadores quimiotácticos e citocinas envolvidos no recrutamento e na activação celular, com repercussão na broncomotricidade e na remodelação da parede brônquica.

Palavras-chave:
Asma
epitélio
inflamação
Abstract

It is done a review of the intervention of the epithelial bronchial cell in the pathophysiology of asthma. The respiratory epithelium acts as a physical barrier that separates the external environment from the pulmonary internal environment. It controls the intercellular and trans-cellular permeability and this way the accessibility of the inhaled pathogens to the antigen presenting cells involved in the immuno-inflammatory response. Epithelial cells connected by tight junctions contribute to the barrier function of the airways. They express a poliovirus receiver – related protein (PRR), toll like receptors (TLRs) and protease-activated receptors (PARs), which recognize bacterial agents and allergens. Its dysfunction turns them into important sources of inflammatory mediators.

The bidirectional interaction between the epithelium and other bronchial wall elements with inhaled particles originates a structure with its own identity, the designated EMTU – Epithelial Mesenchymal Trophic Unit.

These observations support a central role for the epithelial cell in chronic inflammation and in the remodelling of the asthmatic process.

Infectious diseases and environmental stress can activate different cell receptors and signalling pathways that induce changes in the cell surface modifying their response to future stimulations, namely to other infectious aggressions.

The bronchial epithelium has barrier functions with selective permeability; it has metabolic activity producing cytokines and chemokines stimulating the cell's recruitment and activation, increasing the bronchial reactivity and the remodelling of the airways.

Key-words:
Asthma
epithelium
inflammation
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Bibliografia
[1.]
Jean Bousquet, P.K. Jeffery, W.W. Busse, M. Johnson, A.M. Vignola.
Asthma. From bronchoconstriction to airways inflammation and remodeling.
Am J Respir Crit Care Med, 161 (2000), pp. 1720-1745
[2.]
A. Todo-Bom, A. Mota Pinto.
Fisiopatologia da asma grave.
Rev Port Imunoalergol, 14 (2006), pp. 43-48
[3.]
Hamida Hammad, B.N. Lambrecht, H. Hammad, B.N. Lambrecht.
Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation.
J Allergy Clin Immunol, 118 (2006), pp. 331-336
[4.]
H. Kim Chang.
Regulation of FoxP3+ Regulatory T Cells and Th17 cells by retinoids.
Clin Dev Immunol, 416910 (2008), pp. 1-12
[5.]
Mark Larché.
Regulatory T cells in allergy and asthma.
Chest, 132 (2007), pp. 1007-1014
[6.]
Jennifer Kearley, D.S. Robinson, C.M. Lloyd.
CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling.
J Allergy Clin Immunol, 122 (2008), pp. 617-624
[7.]
Angelo Barbato, G. Turato, S. Baraldo, E. Bazzan, F. Calabrese, C. Panizzolo, et al.
Epithelial damage and angio-genesis in the airways of children with asthma.
Am J Respir Crit Care Med, 174 (2006), pp. 975-981
[8.]
Darryl Knight.
Increased permeability of asthmatic epithelial cells to pollutants: does this mean that they are intrinsically abnormal?.
Clin Exp Allergy, 32 (2002), pp. 1263-1265
[9.]
A.B. Vroling, W.J. Fokkens, C.M. van Drunen.
How epithelial cells detect danger: aiding the immune response.
[10.]
Renato Colognato, J.R. Slupsky, M. Jendrach, L. Burysek, T. Syrovets, T. Simmet.
Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells.
Blood, 102 (2003), pp. 2645-2652
[11.]
Hammad Hamida, B.N. Lambrecht.
Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma.
Nature Rev, 8 (2008), pp. 193-204
[12.]
H.Y. Tai, M.F. Tam, H. Chou, H.J. Peng, S.N. Su, D.W. Perng, H.D. Shen.
Pen ch 13 allergen induces secretion of mediators and degradation of occludin protein of human lung epithelial cells.
[13.]
L. Cortes, A.L. Carvalho, A. Todo-Bom, C. Faro, E. Pires, P. Veríssimo.
Purification of a novel aminopeptidase from the pollen of parietária-judaica that alters epithelial integrity and degrades neuropeptides.
J Allergy Clin Immunol, 118 (2006), pp. 878-884
[14.]
Kawai Taro, S. Akira.
Pathogen recognition with Toll-like receptors.
Curr Opin Immunol, 17 (2005), pp. 338-344
[15.]
J. Laurent Geoffrey.
No Bit PARt for PAR-1.
Am J Respir Cell Mol Biol, 33 (2005), pp. 213-215
[16.]
Tomoko Suzuki, T.J. Moraes, E. Vachon, H.H. Ginzberg, T.T. Huang, M.A. Matthay, et al.
Proteinase-activated receptor-1 mediates elastase-induced apoptosis of human lung epithelial cells.
Am J Respir Cell Mol Biol, 33 (2005), pp. 231-247
[17.]
Cory Ebeling, T. Lam, J.R. Gordon, M.D. Hollenberg, H. Vliagoftis.
Proteinase-activated receptor-2 promotes allergic sensitization to an inhaled antigen through a TNF-mediated pathway.
J Immunol, 179 (2007), pp. 2910-2917
[18.]
Rahman Irfan, S.K. Biswas, A. Kode.
Oxidant and antioxidant balance in the airways and airway diseases.
Eur J Pharmacol, 533 (2006), pp. 222-239
[19.]
A. Comhair Susy, P.R. Bhathena, C. Farver, F.B. Thunnissen, S.C. Erzurum.
Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells.
FASEB J, 15 (2001), pp. 70-78
[20.]
Hamida Hammad, A.S. Charbonnier, C. Duez, G.A. Jacquet Astewart, A.B. Tonnel, et al.
TH2 polarization by Der p 1– pulsed monocyte-derived dendritic cells is due to the allergic status of the donors.
Blood, 98 (2001), pp. 1135-1141
[21.]
T. Holgate Stephen.
The epithelium takes centre stage in asthma and atopic dermatitis.
Trends Immunol, 28 (2007), pp. 248-251
[22.]
Masafumi Arima, T. Fukuda.
Novel functions of two chemokines in allergic disease thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22.
Allergy Clin Immunol Int – J World Allergy Org, 18 (2006), pp. 58-64
[23.]
Sun Ying, B. O’Connor, J. Ratoff, Q. Meng, K. Mallett, D. Cousins, et al.
Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity.
J Immunol, 174 (2005), pp. 8183-8190
[24.]
Ana Todo-Bom, A. Mota Pinto, S. Vale Pereira, V. Alves, M. Dourado, M. Santos Rosa.
Substance P in long-lasting asthma: Immunoinflammatory pathways.
Allergy Clin Immunol Int – J World Allergy Org, 18 (2006), pp. 242-248
[25.]
Jochen Springer, D.A. Groneberg, R. Pregla, A. Fischer.
Inflammatory cells as source of tachykinin-induced mucus secretion in chronic bronchitis.
Regul Pept, 124 (2005), pp. 195-201
[26.]
T. Holgate Stephen, D.E. Davies, P.M. Lackie, S.J. Wilson, S.M. Puddicombe, J.L. Lordan.
Epithelial-mesenchymal interactions in the pathogenesis of asthma.
J Allergy Clin Immunol, 105 (2000), pp. 193-204
[27.]
Tillie-Louise Hackett, D.A. Knight.
The role of epithelial injury and repair in the origins of asthma.
Curr Opin Allergy Clin Immunol, 7 (2007), pp. 63-68
[28.]
Y. Tesfaigzi.
Processes involved in the repair of injured airway epithelia.
Arch Immunol Ther Exp (Warsz), 51 (2003), pp. 283-288
[29.]
Zoulfia Allakhverdi, M.R. Comeau, H.K. Jessup, B.R. Yoon, A. Brewer, S. Chartier, et al.
Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells.
J Exp Med, 204 (2007), pp. 253-258
[30.]
Yong-Jun Liu, V. Soumelis, N. Watanabe, T. Ito, Y.H. Wang, R.W. Malefyt, et al.
TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation.
Annu Rev Immunol, 25 (2007), pp. 193-219
[31.]
J. Leonard Warren.
TSLP: finally in the limelight.
Nature Immunol, 3 (2002), pp. 605-607
[32.]
I.A. Fedorov, S.J. Wilson, D.E. Davies, S.T. Holgate.
Epithelial stress and structural remodelling in childhood asthma.
Thorax, 60 (2005), pp. 389-394
[33.]
Andrea Zanini, A. Chetta, M. Saetta, S. Baraldo, R. D’Ippolito, A. Castagnaro, et al.
Chymase-positive mast cells play a role in the vascular component of airway remodeling in asthma.
J Allergy Clin Immunol, 120 (2007), pp. 329-333
[34.]
Shaoli Zhang, H. Smartt, S.T. Holgate, W.R. Roche.
Growth factors secreted by bronchial epithelial cells control myofibroblast proliferation: an in vitro co-culture model of airway remodeling in asthma.
Lab Invest, 79 (1999), pp. 395-405
[35.]
Simon Phipps, F. Benyahia, T.T. Ou, J. Barkans, D.S. Robinson, A.B. Kay.
Acute allergen-induced airway remodeling in atopic asthma.
Am J Respir Cell Mol Biol, 31 (2004), pp. 626-632
[36.]
C. Willis Brigham, Z. Borok.
TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease.
Am J Physiol Lung Cell Mol Physiol, 293 (2007), pp. L525-L534
[37.]
Nihlberg Kristian, K. Larsen, A. Hultgardh-Nilsson, A. Malmstrom, L. Bjermer, G. Westergren-Thorsson.
Tissue fibrocytes in patients with mild asthma: a possible link to thickness of reticular basement membrane?.
Respir Res, 7 (2006), pp. 50
[38.]
Yin Chen, Y.H. Zhao, Y.P. Di, R. Wu.
Characterization of human mucin 5B gene expression in airway epithelium and the genomic clone of the amino-terminal and 5-flanking region.
Am J Respir Cell Mol Biol, 25 (2001), pp. 542-553
[39.]
Pierre-Regis Burgel, D. Montani, C. Danel, D.J. Dusser, J.A. Nadel.
A morphometric study of mucins and small airway plugging in cystic fibrosis.
Thorax, 62 (2007), pp. 153-161
[40.]
S. Deshmukh Hitesh, L.M. Case, S.C. Wesselkamper, M.T. Borchers, L.D. Martin, H.G. Shertzer, et al.
Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation.
Am J Respir Crit Care Med, 171 (2005), pp. 305-314
[41.]
L. Lordan James, F. Bucchieri, A. Richter, A. Konstantinidis, J.W. Holloway, M. Thornber, et al.
Cooperative effects of Th2 cytokines and allergen on normal and asthmatic bronchial epithelial cells.
J Immunol, 169 (2002), pp. 407-414
[42.]
Beiyun Zhou, D.K. Ann, X. Li, K.J. Kim, H. Lin, P. Minoo, et al.
Hypertonic induction of aquaporin-5: novel role of hypoxia-inducible factor-1.
Am J Physiol Cell Physiol, 292 (2007), pp. C1280-C1290
[43.]
K. Sidhaye Venkataramana, K.S. Schweitzer, M.J. Caterina, L. Shimoda, L.S. King.
Shear stress regulates aquaporin-5 and airway epithelial barrier function.
PNAS, 105 (2008), pp. 3345-3350
[44.]
A. O’Neill Luke, A.G. Bowie.
The family of five: TIR domain-containing adaptors in Toll-like receptor signalling.
Nat Rev Immunol, 7 (2007), pp. 353-364
[45.]
Rae Wright Jo.
The “wisdom” of lung surfactant: balancing host defense and surface tension-reducing functions.
Am J Physiol Lung Cell Mol Physiol, 291 (2006), pp. L847-L850
[46.]
Andre Fleer, T.G. Krediet.
Innate immunity: toll-like receptors and some more. a brief history, basic organization and relevance for the human newborn.
Neonatology, 92 (2007), pp. 145-157
[47.]
A. McCullers Jonathan, K.C. Bartmess.
Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae.
J Infect Dis, 187 (2003), pp. 1000-1009
[48.]
R. Bai Tony, D.A. Knight.
Structural changes in the airways in asthma observations and consequences.
Clin Sci (Lond), 108 (2005), pp. 463-477
[49.]
J. Ratner Adam, E.S. Lysenko, M.N. Paul, J.N. Weiser.
Synergistic proinflammatory responses induced by polymicrobial colonization of epithelial surfaces.
Proc Natl Acad Sci (USA), 102 (2005), pp. 3429-3434
[50.]
J. Goulding, R. Snelgrove, J. Saldana, A. Didierlaurent, M. Cavanagh, E. Gwyer, et al.
Respiratory infections. Do we ever recover?.
Proc Am Thorac Soc, 4 (2007), pp. 618-625
[51.]
J.S. Torday, V.K. Rehan.
The evolutionary continuum from lung development to homeostasis and repair.
Am J Physiol Lung Cell Mol Physiol, 292 (2007), pp. L608-L611
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