RT Journal Article SR Electronic T1 microRNA-mediated inhibition of IL-8 production from cystic fibrosis bronchial epithelial cells JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P2104 VO 42 IS Suppl 57 A1 Kevin Gaughan A1 Tidi Hassan A1 Raman Agarwal A1 Marcus Mall A1 Noel McElvaney A1 Catherine Greene YR 2013 UL http://erj.ersjournals.com/content/42/Suppl_57/P2104.abstract AB The pulmonary manifestations of cystic fibrosis (CF) are characterized by abnormally high levels of infiltrating neutrophils largely due to aberrant expression of interleukin-8 (IL-8) by airway epithelial cells. Thus inhibiting IL-8 expression within the CF lung represents an anti-inflammatory strategy. MicroRNAs (miRs) are post-transcriptional negative regulators. Overexpression of miRs is possible by the use of premiR mimetics. Here we profiled miRNA expression in CF vs. non CF endobronchial brushings (n=5 each) and CFBE41o- vs. 16HBE14o- bronchial epithelial cells lines. We identified a selection of lead miRs that are predicted to regulate IL-8 in silico and are under expressed in CF bronchial epithelium in vitro and in vivo. Based on further bioinformatic analysis and validation studies using an IL-8 3’UTR luciferase reporter we focused on four specific miRs. Levels of these miRs were quantified in whole lung homogenates from wild type (WT) and betaENaC-overexpressing (betaENaC-Tg) mice. All miRs were marginally decreased in the betaENaC-Tg compared to WT mice at 2 and 6 weeks of age, with miR-200b significantly lower at 6 weeks (*p<0.05). The KI of each premiR was calculated and collectively, a premiR-mix containing K0.25 for each miR inhibited basal (*p<0.05) and LPS-induced (***p<0.001) IL-8 protein production from CFBE41o- cells grown in monolayers. There was no off target effect on Cyclin D1(CCND1) protein expression; CCND1 is predicted to be regulated by two of the four miRs. These results indicate that aberrant IL-8 production by CF bronchial epithelial cells may have the potential to be corrected using miR-based medicines.