PT - JOURNAL ARTICLE AU - Sinéad Weldon AU - Qiwei Chen AU - Irene Oglesby AU - Christine Wohlford-Lenane AU - Jennifer Bartlett AU - Gerry McElvaney AU - Stuart Elborn AU - Paul McCray, Jr AU - Catherine Greene AU - Clifford Taggart TI - Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas DP - 2012 Sep 01 TA - European Respiratory Journal PG - 4739 VI - 40 IP - Suppl 56 4099 - http://erj.ersjournals.com/content/40/Suppl_56/4739.short 4100 - http://erj.ersjournals.com/content/40/Suppl_56/4739.full SO - Eur Respir J2012 Sep 01; 40 AB - Apoptosis is a physiological process essential for homeostasis of epithelial organisation and function. Cystic fibrosis (CF) lung disease is characterised by chronic infection and inflammation and previous work suggests that apoptosis is dysfunctional in the CF airways with conflicting results. In addition, controversy exists regarding how CFTR misfolding contributes to apoptosis. In this study, we evaluated the relationship between CFTR mutation and apoptosis in CF airway epithelial cells. Basal activity of the executioner caspase, caspase-3, was significantly increased in CF tracheal and bronchial epithelial cell lines and primary bronchial epithelial cells compared to non-CF controls. In addition, activity of the upstream initiator caspase, caspase-8, was significantly increased in CF epithelial cells compared to controls, suggesting involvement of extrinsic apoptosis signalling, which is mediated by the activation of death receptors, such as Fas (CD95). Increased levels of Fas were observed in CF epithelial cells and bronchial brushings, reciprocal decreases in a selection of microRNAs predicted to target Fas were evident in the brushing samples, and neutralization of Fas significantly inhibited caspase-3 activity in CF epithelial cells compared to untreated cells. Furthermore, activation of Fas significantly increased caspase-3 activity and apoptosis in CF epithelial cells compared to control cells. Overall, these results suggest that CF airway epithelial cells are more sensitive to apoptosis via increased levels of Fas and subsequent activation of the Fas death receptor pathway. Further work will delineate the mechanism underlying increased Fas expression in CF epithelial cells.