IL‐22 increases CFTR expression and host defence capacity of airway epithelial cells

Abstract

Interleukin (IL)‐22 is a pleiotropic cytokine which predominately targets epithelial cells. IL‐22 has been implicated in increasing epithelial host defence via a number of different mechanisms and we hypothesized its IL‐22 application would stimulate several protective mechanisms in airway epithelial cells. Using the model human airway bronchial epithelial cell line 16HBEo− we investigated the ability of IL‐22 to increase CFTR expression, and determined that treatment for 24 hours increased CFTR gene and protein expression, resulting in increased CFTR activity measured via iodide efflux assays. Furthermore, IL‐22 increased mRNA expression for the anti‐microbial peptides human beta‐defensin‐2 (hDB‐2) and neutrophil gelatinase‐associated lipocalin (NGAL), but had no effect on expression of the cathelicidin LL‐37. Additionally, we investigated the ability of IL‐22 to enhance epithelial repair using a mechanical wounding model, and determined that its presence significantly enhanced would healing in this model. IL‐22 application was associated with increased STAT‐3 phosphorylation. This is the first report of IL‐22 acting to increase CFTR expression and functionality, which together with its ability to increase anti‐microbial peptide expression and would healing ability, confirm its role as a potentially important factor in the airway epithelial host defence and repair. CFCanada and NSERC.