{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:49:36Z","timestamp":1790794176769,"version":"4.1.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Richard and Edith Strauss Foundation","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Asthma is a heterogenous disease characterized by chronic inflammation and airway remodeling. An increase in the severity of airway remodeling is associated with a more severe form of asthma. There is increasing interest in the epithelial to mesenchymal transition process and mechanisms involved in the differentiation and repair of the airway epithelium, especially as they apply to severe asthma. Growing evidence suggests that Epithelial-Mesenchymal transition (EMT) could contribute to airway remodeling and fibrosis in asthma. Severe asthmatic patients with remodeled airways have a neutrophil driven inflammation. Neutrophils are an important source of TGF-\u03b21, which plays a role in recruitment and activation of inflammatory cells, extracellular matrix (ECM) production and fibrosis development, and is a potent inducer of EMT.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>As there is little data examining the contribution of neutrophils and\/or their mediators to the induction of EMT in airway epithelial cells, the objective of this study was to better understand the potential role of neutrophils in severe asthma in regards to EMT.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We used an in vitro system to investigate the neutrophil-epithelial cell interaction. We obtained peripheral blood neutrophils from severe asthmatic patients and control subjects and examined for their ability to induce EMT in primary airway epithelial cells.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Our data indicate that neutrophils from severe asthmatic patients induce changes in morphology and EMT marker expression in bronchial epithelial cells consistent with the EMT process when co-cultured. TGF-\u03b21 levels in the culture medium of severe asthmatic patients were increased compared to that from co-cultures of non-asthmatic neutrophils and epithelial cells.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions and clinical relevance<\/jats:title>\n                <jats:p>As an inducer of EMT and an important source of TGF-\u03b21, neutrophils may play a significant role in the development of airway remodeling and fibrosis in severe asthmatic airways.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-019-1186-8","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T20:44:07Z","timestamp":1572468247000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Neutrophils from severe asthmatic patients induce epithelial to mesenchymal transition in healthy bronchial epithelial cells"],"prefix":"10.1186","volume":"20","author":[{"given":"Alexandre","family":"Haddad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mellissa","family":"Gaudet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Plesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoulfia","family":"Allakhverdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea K.","family":"Mogas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Audusseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn J.","family":"Baglole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Eidelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Olivenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara S.","family":"Ludwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qutayba","family":"Hamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,29]]},"reference":[{"key":"1186_CR1","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1146\/annurev-pathol-012414-040343","volume":"10","author":"HE Trejo Bittar","year":"2015","unstructured":"Trejo Bittar HE, Yousem SA, Wenzel SE. Pathobiology of severe asthma. Annu Rev Pathol. 2015;10:511\u201345.","journal-title":"Annu Rev Pathol"},{"issue":"1","key":"1186_CR2","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nri3786","volume":"15","author":"JV Fahy","year":"2015","unstructured":"Fahy JV. Type 2 inflammation in asthma [mdash] present in most, absent in many. Nat Rev Immunol. 2015;15(1):57\u201365.","journal-title":"Nat Rev Immunol"},{"issue":"5","key":"1186_CR3","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1111\/j.1365-2222.2011.03929.x","volume":"42","author":"S Wenzel","year":"2012","unstructured":"Wenzel S. Severe asthma: from characteristics to phenotypes to endotypes. Clin Exp Allergy. 2012;42(5):650\u20138.","journal-title":"Clin Exp Allergy"},{"issue":"9537","key":"1186_CR4","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/S0140-6736(06)69288-X","volume":"368","author":"ST Holgate","year":"2006","unstructured":"Holgate ST, Polosa R. The mechanisms, diagnosis, and management of severe asthma in adults. Lancet. 2006;368(9537):780\u201393.","journal-title":"Lancet"},{"issue":"3","key":"1186_CR5","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1164\/ajrccm.160.3.9812110","volume":"160","author":"SE Wenzel","year":"1999","unstructured":"Wenzel SE, Schwartz LB, Langmack EL, Halliday JL, Trudeau JB, Gibbs RL, et al. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Respir Crit Care Med. 1999;160(3):1001\u20138.","journal-title":"Am J Respir Crit Care Med"},{"issue":"10","key":"1186_CR6","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1136\/thorax.57.10.875","volume":"57","author":"R Green","year":"2002","unstructured":"Green R, Brightling C, Woltmann G, Parker D, Wardlaw A, Pavord I. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax. 2002;57(10):875\u20139.","journal-title":"Thorax"},{"issue":"5","key":"1186_CR7","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1067\/mai.2001.119411","volume":"108","author":"PG Woodruff","year":"2001","unstructured":"Woodruff PG, Khashayar R, Lazarus SC, Janson S, Avila P, Boushey HA, et al. Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma. J Allergy Clin Immunol. 2001;108(5):753\u20138.","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"1186_CR8","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1378\/chest.09-0174","volume":"136","author":"S Gupta","year":"2009","unstructured":"Gupta S, Siddiqui S, Haldar P, Raj JV, Entwisle JJ, Wardlaw AJ, et al. Qualitative analysis of high-resolution CT scans in severe asthma. CHEST Journal. 2009;136(6):1521\u20138.","journal-title":"CHEST Journal"},{"issue":"12","key":"1186_CR9","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1164\/rccm.2108069","volume":"166","author":"AL James","year":"2002","unstructured":"James AL, Maxwell PS, Pearce-Pinto G, Elliot JG, Carroll NG. The relationship of reticular basement membrane thickness to airway wall remodeling in asthma. Am J Respir Crit Care Med. 2002;166(12):1590\u20135.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"1186_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1136\/thx.17.1.69","volume":"17","author":"B Naylor","year":"1962","unstructured":"Naylor B. The shedding of the mucosa of the bronchial tree in asthma. Thorax. 1962;17(1):69\u201372.","journal-title":"Thorax"},{"key":"1186_CR11","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1164\/ajrccm\/147.2.405","volume":"147","author":"N Carroll","year":"1993","unstructured":"Carroll N, Elliot J, Morton A, James A. The Strudure of large and small Airways in Nonfatal and Fatal Asthma. Am Rev Respir Dis. 1993;147:405\u201310.","journal-title":"Am Rev Respir Dis"},{"issue":"4","key":"1186_CR12","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1378\/chest.101.4.916","volume":"101","author":"T Aikawa","year":"1992","unstructured":"Aikawa T, Shimura S, Sasaki H, Ebina M, Takishima T. Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest. 1992;101(4):916\u201321.","journal-title":"Chest"},{"issue":"12","key":"1186_CR13","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1164\/rccm.200306-727OC","volume":"168","author":"H Tanaka","year":"2003","unstructured":"Tanaka H, Yamada G, Saikai T, Hashimoto M, Tanaka S, Suzuki K, et al. Increased airway vascularity in newly diagnosed asthma using a high-magnification bronchovideoscope. Am J Respir Crit Care Med. 2003;168(12):1495\u20139.","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"1186_CR14","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1378\/chest.07-2779","volume":"134","author":"RS Aysola","year":"2008","unstructured":"Aysola RS, Hoffman EA, Gierada D, Wenzel S, Cook-Granroth J, Tarsi J, et al. Airway remodeling measured by multidetector CT is increased in severe asthma and correlates with pathology. CHEST. 2008;134(6):1183\u201391.","journal-title":"CHEST"},{"issue":"2","key":"1186_CR15","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/cr.2009.5","volume":"19","author":"J Xu","year":"2009","unstructured":"Xu J, Lamouille S, Derynck R. TGF-\u03b2-induced epithelial to mesenchymal transition. Cell Res. 2009;19(2):156\u201372.","journal-title":"Cell Res"},{"issue":"7","key":"1186_CR16","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1083\/jcb.200601018","volume":"172","author":"JM Lee","year":"2006","unstructured":"Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelial\u2013mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol. 2006;172(7):973\u201381.","journal-title":"J Cell Biol"},{"issue":"20","key":"1186_CR17","doi-asserted-by":"publisher","first-page":"6566","DOI":"10.1093\/nar\/gki965","volume":"33","author":"C Vandewalle","year":"2005","unstructured":"Vandewalle C, Comijn J, De Craene B, Vermassen P, Bruyneel E, Andersen H, et al. SIP1\/ZEB2 induces EMT by repressing genes of different epithelial cell\u2013cell junctions. Nucleic Acids Res. 2005;33(20):6566\u201378.","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"1186_CR18","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1242\/jcs.00389","volume":"116","author":"J Ikenouchi","year":"2003","unstructured":"Ikenouchi J, Matsuda M, Furuse M, Tsukita S. Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins\/occludin by snail. J Cell Sci. 2003;116(10):1959\u201367.","journal-title":"J Cell Sci"},{"issue":"3","key":"1186_CR19","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.3892\/ol.2013.1108","volume":"5","author":"P Chunhacha","year":"2013","unstructured":"Chunhacha P, Sriuranpong V, Chanvorachote P. Epithelial-mesenchymal transition mediates anoikis resistance and enhances invasion in pleural effusion-derived human lung cancer cells. Oncol Lett. 2013;5(3):1043\u20137.","journal-title":"Oncol Lett"},{"issue":"1","key":"1186_CR20","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1093\/molehr\/gal091","volume":"13","author":"U Ullmann","year":"2007","unstructured":"Ullmann U, Gilles C, Sermon K, De Rycke M, Van de Velde H, Van Steirteghem A, et al. Epithelial\u2013mesenchymal transition process in human embryonic stem cells cultured in feeder-free conditions. Mol Hum Reprod. 2007;13(1):21\u201332.","journal-title":"Mol Hum Reprod"},{"issue":"14","key":"1186_CR21","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1161\/CIRCULATIONAHA.111.040352","volume":"125","author":"JC Kovacic","year":"2012","unstructured":"Kovacic JC, Mercader N, Torres M, Boehm M, Fuster V. Epithelial-to-mesenchymal and endothelial-to-mesenchymal transition. Circulation. 2012;125(14):1795\u2013808.","journal-title":"Circulation"},{"issue":"9","key":"1186_CR22","doi-asserted-by":"publisher","first-page":"8094","DOI":"10.1074\/jbc.M413102200","volume":"280","author":"M Zeisberg","year":"2005","unstructured":"Zeisberg M, Shah AA, Kalluri R. Bone morphogenic protein-7 induces mesenchymal to epithelial transition in adult renal fibroblasts and facilitates regeneration of injured kidney. J Biol Chem. 2005;280(9):8094\u2013100.","journal-title":"J Biol Chem"},{"issue":"131","key":"1186_CR23","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1183\/09059180.00004413","volume":"23","author":"M Pain","year":"2014","unstructured":"Pain M, Bermudez O, Lacoste P, Royer P-J, Botturi K, Tissot A, et al. Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype. Eur Respir Rev. 2014;23(131):118\u201330.","journal-title":"Eur Respir Rev"},{"issue":"4","key":"1186_CR24","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1165\/rcmb.2006-0012OC","volume":"35","author":"K-Y Lee","year":"2006","unstructured":"Lee K-Y, Ho S-C, Lin H-C, Lin S-M, Liu C-Y, Huang C-D, et al. Neutrophil-derived elastase induces TGF-\u03b21 secretion in human airway smooth muscle via NF-\u03baB pathway. Am J Respir Cell Mol Biol. 2006;35(4):407\u201314.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"3","key":"1186_CR25","doi-asserted-by":"publisher","first-page":"928","DOI":"10.2353\/ajpath.2007.061043","volume":"171","author":"PC Maffia","year":"2007","unstructured":"Maffia PC, Zittermann SE, Scimone ML, Tateosian N, Amiano N, Guerrieri D, et al. Neutrophil elastase converts human immature dendritic cells into transforming growth factor-\u03b21-secreting cells and reduces allostimulatory ability. Am J Pathol. 2007;171(3):928\u201337.","journal-title":"Am J Pathol"},{"issue":"3","key":"1186_CR26","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1681\/ASN.2004050425","volume":"16","author":"DY Rhyu","year":"2005","unstructured":"Rhyu DY, Yang Y, Ha H, Lee GT, Song JS, S-t U, et al. Role of reactive oxygen species in TGF-\u03b21-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells. J Am Soc Nephrol. 2005;16(3):667\u201375.","journal-title":"J Am Soc Nephrol"},{"issue":"3","key":"1186_CR27","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1165\/ajrcmb.17.3.2733","volume":"17","author":"EM Minshall","year":"1997","unstructured":"Minshall EM, Leung DY, Martin RJ, Song YL, Cameron L, Ernst P, et al. Eosinophil-associated TGF-\u03b21 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol. 1997;17(3):326\u201333.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"6","key":"1186_CR28","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1164\/ajrccm.158.6.9712073","volume":"158","author":"HW Chu","year":"1998","unstructured":"Chu HW, Halliday JL, Martin RJ, Leung DY, Szefler SJ, Wenzel SE. Collagen deposition in large airways may not differentiate severe asthma from milder forms of the disease. Am J Respir Crit Care Med. 1998;158(6):1936\u201344.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"1186_CR29","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1164\/ajrccm.156.2.9609066","volume":"156","author":"AM Vignola","year":"1997","unstructured":"Vignola AM, Chanez P, Chiappara G, Merendino A, Pace E, Rizzo A, et al. Transforming growth factor-\u03b2 expression in mucosal biopsies in asthma and chronic bronchitis. Am J Respir Crit Care Med. 1997;156(2):591\u20139.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"1186_CR30","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1164\/ajrccm.156.2.9605065","volume":"156","author":"AE Redington","year":"1997","unstructured":"Redington AE, Madden J, Frew AJ, Djukanovic R, Roche WR, Holgate ST, et al. Transforming growth factor-\u03b2 1 in asthma: measurement in bronchoalveolar lavage fluid. Am J Respir Crit Care Med. 1997;156(2):642\u20137.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"1186_CR31","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1164\/rccm.200811-1730OC","volume":"180","author":"T-L Hackett","year":"2009","unstructured":"Hackett T-L, Warner SM, Stefanowicz D, Shaheen F, Pechkovsky DV, Murray LA, et al. Induction of epithelial\u2013mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-\u03b21. Am J Respir Crit Care Med. 2009;180(2):122\u201333.","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"1186_CR32","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1164\/ajrccm.156.3.9610046","volume":"156","author":"SE Wenzel","year":"1997","unstructured":"Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma: persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med. 1997;156(3):737\u201343.","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"1186_CR33","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1378\/chest.07-1047","volume":"132","author":"DE Shaw","year":"2007","unstructured":"Shaw DE, Berry MA, Hargadon B, McKenna S, Shelley MJ, Green RH, et al. Association between neutrophilic airway inflammation and airflow limitation in adults with asthma. CHEST. 2007;132(6):1871\u20135.","journal-title":"CHEST"},{"issue":"1","key":"1186_CR34","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/0167-5699(95)80066-2","volume":"16","author":"MA Cassatella","year":"1995","unstructured":"Cassatella MA. The production of cytokines by polymorphonuclear neutrophils. Immunol Today. 1995;16(1):21\u20136.","journal-title":"Immunol Today"},{"issue":"2","key":"1186_CR35","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/jcp.1041400226","volume":"140","author":"GR Grotendorst","year":"1989","unstructured":"Grotendorst GR, Smale G, Pencev D. Production of transforming growth factor beta by human peripheral blood monocytes and neutrophils. J Cell Physiol. 1989;140(2):396\u2013402.","journal-title":"J Cell Physiol"},{"issue":"15","key":"1186_CR36","doi-asserted-by":"publisher","first-page":"6805","DOI":"10.1073\/pnas.88.15.6805","volume":"88","author":"J Reibman","year":"1991","unstructured":"Reibman J, Meixler S, Lee TC, Gold LI, Cronstein BN, Haines KA, et al. Transforming growth factor beta 1, a potent chemoattractant for human neutrophils, bypasses classic signal-transduction pathways. Proc Natl Acad Sci. 1991;88(15):6805\u20139.","journal-title":"Proc Natl Acad Sci"},{"issue":"3","key":"1186_CR37","first-page":"313","volume":"43","author":"M Lagraoui","year":"1997","unstructured":"Lagraoui M, Gagnon L. Enhancement of human neutrophil survival and activation by TGF-beta 1. Cell Mol Biol (Noisy-le-Grand, France). 1997;43(3):313\u20138.","journal-title":"Cell Mol Biol (Noisy-le-Grand, France)"},{"key":"1186_CR38","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1084\/jem.173.5.1121","volume":"173","author":"RA Fava","year":"1991","unstructured":"Fava RA, Olsen NJ, Postlethwaite AE, Broadley KN, Davidson J, Nanney L, et al. Transforming growth factor b1 (TGF-b1) induced neutrophil recruitment to synovial tissues: implications for TGF-b-driven synovial inflammation and hyperplasia. J Exp Med. 1991;173:1121\u201332.","journal-title":"J Exp Med"},{"issue":"6","key":"1186_CR39","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1067\/mai.2000.110556","volume":"106","author":"HW Chu","year":"2000","unstructured":"Chu HW, Trudeau JB, Balzar S, Wenzel SE. Peripheral blood and airway tissue expression of transforming growth factor \u03b2 by neutrophils in asthmatic subjects and normal control subjects. J Allergy Clin Immunol. 2000;106(6):1115\u201323.","journal-title":"J Allergy Clin Immunol"},{"issue":"5","key":"1186_CR40","doi-asserted-by":"publisher","first-page":"e64281","DOI":"10.1371\/journal.pone.0064281","volume":"8","author":"A Yasukawa","year":"2013","unstructured":"Yasukawa A, Hosoki K, Toda M, Miyake Y, Matsushima Y, Matsumoto T, et al. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells. PLoS One. 2013;8(5):e64281.","journal-title":"PLoS One"},{"issue":"9","key":"1186_CR41","doi-asserted-by":"publisher","first-page":"1805","DOI":"10.1158\/1535-7163.MCT-12-1007","volume":"12","author":"C Larocca","year":"2013","unstructured":"Larocca C, Cohen JR, Fernando RI, Huang B, Hamilton DH, Palena C. An autocrine loop between TGF-\u03b21 and the transcription factor brachyury controls the transition of human carcinoma cells into a mesenchymal phenotype. Mol Cancer Ther. 2013;12(9):1805\u201315.","journal-title":"Mol Cancer Ther"},{"issue":"3","key":"1186_CR42","first-page":"L525","volume":"293","author":"BC Willis","year":"2007","unstructured":"Willis BC, Borok Z. TGF-\u03b2-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Phys Lung Cell Mol Phys. 2007;293(3):L525\u2013L34.","journal-title":"Am J Phys Lung Cell Mol Phys"},{"issue":"5","key":"1186_CR43","doi-asserted-by":"publisher","first-page":"F1202","DOI":"10.1152\/ajprenal.00406.2005","volume":"290","author":"NG Docherty","year":"2006","unstructured":"Docherty NG, O'Sullivan OE, Healy DA, Murphy M, O'Neill AJ, Fitzpatrick JM, et al. TGF-\u03b2 1-induced EMT can occur independently of its proapoptotic effects and is aided by EGF receptor activation. Am J Physiol Renal Physiol. 2006;290(5):F1202\u2013F12.","journal-title":"Am J Physiol Renal Physiol"},{"issue":"6","key":"1186_CR44","first-page":"L1120","volume":"297","author":"G Zhou","year":"2009","unstructured":"Zhou G, Dada LA, Wu M, Kelly A, Trejo H, Zhou Q, et al. Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1. Am J Phys Lung Cell Mol Phys. 2009;297(6):L1120\u2013L30.","journal-title":"Am J Phys Lung Cell Mol Phys"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-019-1186-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12931-019-1186-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-019-1186-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T00:26:34Z","timestamp":1603844794000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-019-1186-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,29]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1186"],"URL":"https:\/\/doi.org\/10.1186\/s12931-019-1186-8","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,29]]},"assertion":[{"value":"23 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Lung epithelial cells were isolated from lungs obtained by the International Institute for the Advancement of Medicine. Neutrophils were isolated from the blood of healthy and asthmatic donors where all subjects gave written consent and this research was approved by the McGill University Health Center Ethics Review Board.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AH, MG, MP, ZA, AM, SA, CB, DE, QH and ML declare that they have no competing interests. RO received fees for lectures and as a consultant on advisory boards for Astra Zeneca, Boehringer-Ingelheim, Glaxo Smith Kline, Merck Frosst, Novartis, Sanofi and Teva and has also received funding for research from Astra Zeneca, Glaxo Smith Kline, Chiesi, Sanofi and Boston Scientific.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"234"}}