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Using microarray analysis of bronchial biopsy samples from patients with COPD and controls, we identified\n                    <jats:italic>Wnt4<\/jats:italic>\n                    as being up\u2010regulated in COPD. Analysis of bronchial biopsy samples showed a very strong correlation between\n                    <jats:italic>Wnt4<\/jats:italic>\n                    and\n                    <jats:italic>IL8<\/jats:italic>\n                    gene expression, suggesting that Wnt4 plays a role in chronic lung inflammation.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , Wnt4 induced proliferation and inflammation in human epithelial cells (BEAS\u20102B) and normal primary human bronchial epithelial cells in a concentration\u2010dependent manner. This effect was enhanced in the presence of interleukin\u20101\u03b2 (IL\u20101\u03b2) as a result of activation of the p38 and c\u2010Jun NH\n                    <jats:sub>2<\/jats:sub>\n                    \u2010terminal kinase mitogen\u2010activated protein kinase pathways. Hydrogen peroxide, but not proinflammatory stimuli, up\u2010regulated\n                    <jats:italic>Wnt4<\/jats:italic>\n                    expression in epithelial cells. In monocytic THP\u20101 and primary airway smooth muscle cells, Wnt4 induced inflammation and enhanced the inflammatory response to lipopolysaccharide and IL\u20101\u03b2 but did not induce proliferation. In addition, these other cell types did not have enhanced\n                    <jats:italic>Wnt4<\/jats:italic>\n                    expression in response to hydrogen peroxide. Our results indicate that airway epithelial activation, due to oxidative stress, may lead to\n                    <jats:italic>Wnt4<\/jats:italic>\n                    induction. Wnt4, in turn, acts through the noncanonical pathway to activate epithelial cell remodeling and\n                    <jats:italic>IL8<\/jats:italic>\n                    gene expression, leading to neutrophil infiltration and inflammation.\u2014Durham, A. L., McLaren, A., Hayes, B. P., Caramori, G., Clayton, C. L., Barnes, P. J., Chung, K. F., Adcock, I. M. Regulation of Wnt4 in chronic obstructive pulmonary disease.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 2367\u20132381 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-217083","type":"journal-article","created":{"date-parts":[[2013,3,6]],"date-time":"2013-03-06T00:26:11Z","timestamp":1362529571000},"page":"2367-2381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Regulation of Wnt4 in chronic obstructive pulmonary disease"],"prefix":"10.1096","volume":"27","author":[{"given":"Andrew L.","family":"Durham","sequence":"first","affiliation":[{"name":"Airway Disease Section National Heart and Lung Institute Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"McLaren","sequence":"additional","affiliation":[{"name":"Core Discovery Technology Group GlaxoSmithKline Research Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Hayes","sequence":"additional","affiliation":[{"name":"Allergy and Inflammation Group Respiratory Centre of Excellence for Drug Discovery GlaxoSmithKline Research Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Caramori","sequence":"additional","affiliation":[{"name":"Section of Respiratory Diseases, Centro per lo Studio delle Malattie Infiammatorie Croniche delle Vie Aeree e Patologie Fumo Correlate dell'Apparato Respiratorio Department of Medical Sciences University of Ferrara Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris L.","family":"Clayton","sequence":"additional","affiliation":[{"name":"Core Discovery Technology Group GlaxoSmithKline Research Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Airway Disease Section National Heart and Lung Institute Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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