TY - JOUR T1 - miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production JF - European Respiratory Journal JO - Eur Respir J SP - 1350 LP - 1360 DO - 10.1183/09031936.00163414 VL - 46 IS - 5 AU - Irene K. Oglesby AU - Sebastian F. Vencken AU - Raman Agrawal AU - Kevin Gaughan AU - Kevin Molloy AU - Gerard Higgins AU - Paul McNally AU - Noel G. McElvaney AU - Marcus A. Mall AU - Catherine M. Greene Y1 - 2015/11/01 UR - http://erj.ersjournals.com/content/46/5/1350.abstract N2 - Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis.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 βENaC-transgenic, cystic fibrosis transmembrane conductance regulator (Cftr)-/- and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosis versus non-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide, Pseudomonas-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured.miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, βENaC-transgenic mice and bronchial epithelial cells chronically stimulated with Pseudomonas-conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o− tracheal, CFBE41o− and/or IB3 bronchial epithelial cells.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.Overexpression of miR-17 in cystic fibrosis airway epithelial cells decreases interleukin-8 protein production http://ow.ly/MZbXB ER -