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Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis.<\/jats:p><jats:p>IL-8 protein and mRNA were measured in cystic fibrosis and non-cystic fibrosis bronchoalveolar lavage fluid and bronchial brushings (n=20 per group). miRNAs decreased in the cystic fibrosis lung and predicted to target IL-8 mRNA were quantified in \u03b2ENaC-transgenic, cystic fibrosis transmembrane conductance regulator (<jats:italic>Cftr<\/jats:italic>)<jats:italic>-\/-<\/jats:italic>and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosis<jats:italic>versus<\/jats:italic>non-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide,<jats:italic>Pseudomonas<\/jats:italic>-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured.<\/jats:p><jats:p>miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, \u03b2ENaC-transgenic mice and bronchial epithelial cells chronically stimulated with<jats:italic>Pseudomonas<\/jats:italic>-conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o<jats:sup>\u2212<\/jats:sup>tracheal, CFBE41o<jats:sup>\u2212<\/jats:sup>and\/or IB3 bronchial epithelial cells.<\/jats:p><jats:p>These results implicate defective CFTR, inflammation, neutrophilia and mucus overproduction in regulation of miR-17. Modulating miR-17 expression in cystic fibrosis bronchial epithelial cells may be a novel anti-inflammatory strategy for cystic fibrosis and other chronic inflammatory airway diseases.<\/jats:p>","DOI":"10.1183\/09031936.00163414","type":"journal-article","created":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T19:23:44Z","timestamp":1438889024000},"page":"1350-1360","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":80,"title":["miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production"],"prefix":"10.1183","volume":"46","author":[{"given":"Irene K.","family":"Oglesby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian F.","family":"Vencken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Gaughan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Molloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"McNally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel G.","family":"McElvaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus A.","family":"Mall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Greene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2015,7,9]]},"reference":[{"key":"2024102023363060000_46.5.1350.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043184"},{"key":"2024102023363060000_46.5.1350.2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00228013"},{"key":"2024102023363060000_46.5.1350.3","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.12.2.145"},{"key":"2024102023363060000_46.5.1350.4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115738"},{"key":"2024102023363060000_46.5.1350.5","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0176OC"},{"key":"2024102023363060000_46.5.1350.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.06.047"},{"key":"2024102023363060000_46.5.1350.7","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00426.2012"},{"key":"2024102023363060000_46.5.1350.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature09267"},{"key":"2024102023363060000_46.5.1350.9","doi-asserted-by":"publisher","DOI":"10.1101\/gr.082701.108"},{"key":"2024102023363060000_46.5.1350.10","doi-asserted-by":"publisher","DOI":"10.1586\/eri.11.175"},{"key":"2024102023363060000_46.5.1350.11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902669"},{"key":"2024102023363060000_46.5.1350.12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.204131"},{"key":"2024102023363060000_46.5.1350.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002080107"},{"key":"2024102023363060000_46.5.1350.14","unstructured":"Wei T , Xu N , Meisgen F , et al. 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