Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas (CD95)

Qiwei Chen, Sudha Priya Soundara Pandi, Lauren Kerrigan, Noel G. McElvaney, Catherine M. Greene , J. Stuart Elborn, Clifford C. Taggart, Sinead Weldon

Research output: Contribution to journalArticle

3 Citations (Scopus)
147 Downloads (Pure)

Abstract

Background
Previous work suggests that apoptosis is dysfunctional in cystic fibrosis (CF) airways with conflicting results. We evaluated the relationship between dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and apoptosis in CF airway epithelial cells.

Methods
Apoptosis and associated caspase activity were analysed in non-CF and CF tracheal and bronchial epithelial cell lines.

Results
Basal levels of apoptosis and activity of caspase-3 and caspase-8 were 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 from CF patients compared to non-CF controls. Neutralisation of Fas significantly inhibited caspase-3 activity in CF epithelial cells compared to untreated cells. In addition, activation of Fas significantly increased caspase-3 activity and apoptosis in CF epithelial cells compared to control cells.

Conclusions
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, which may be associated with dysfunctional CFTR.
Original languageEnglish
Pages (from-to)616-623
JournalJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
Volume17
Issue number5
Early online date02 Mar 2018
DOIs
Publication statusPublished - 01 Sep 2018

Keywords

  • Apoptosis
  • Epithelial cells
  • Fas

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas (CD95)'. Together they form a unique fingerprint.

  • Cite this