The Role of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Recognition of Pseudomonas aeruginosa in Lung Epithelial Cells

Cystic Fibrosis Transmembrane Regulator (CFTR) plays an important role in chloride and thiocyanate ion homeostasis in human epithelial surfaces. Deletion of phenylalanine at position 508 (Δ508) leads to cystic fibrosis and dysregulation of pro-inflammatory cytokines. Pseudomonas aeruginosa gains predominance, contributing over 80% of the lung bacteria in adults with CF and this strongly correlates with the decline of pulmonary function and mortality. The research aimed at understanding the role of CFTR in response to P. aeruginosa, (the most common pathogen that colonises the airways of Cystic Fibrosis patients), with the objectives of evaluating the relative expression of epithelial and inflammatory cytokines (IL-17C and IL-6) in five (Calu3, CFBE41o, CFBE41o wt, Calu3 altered and Calu3 knockout) human bronchial epithelial cell lines after two hours of infection with P. aeruginosa using Quantitative Polymerase Chain Reaction (qPCR). It was found that Calu3 and Calu3 altered, treated cell lines significantly (p=0.05) increased in the level of IL-17C and IL-6 mRNA in all the experimental repeats compare to untreated.

The other three (CFBE 41o, CFBE41o wt, and Calu3 knockout) cell lines deficient of CFTR expressed low levels of these cytokines, but the level varied among the experiment in both treated and untreated cells suggesting that CFTR may modulate the level of cytokine production in bronchial epithelial cell lines. CFTR mutations have a direct effect on T cell function; enhance Th17 response which is one of the sources of IL-17. The IL-17C plays a central role in pulmonary host defence by orchestrating the accumulation and associated activity of neutrophils in the bronchoalveolar space. However, the massive neutrophils accumulation in the CF lung does not correlate with bacterial eradication but rather causes extensive tissue damage and inflammation disproportion to infection indicating that the function of neutrophils is dysregulated in CF. Therefore, knocking down IL-17C may minimise inflammation in CF patients.