Interleukin-10 Inhibits Elevated Chemokine Interleukin-8 and Regulated on Activation Normal T Cell Expressed and Secreted Production in Cystic Fibrosis Bronchial Epithelial Cells by Targeting the I kB Kinase α/β Complex

Abstract

Accumulating evidence suggests that in cystic fibrosis (CF) patients, airway fluids are characterized by decreased antibacterial activity, elevated NaCl concentration, and high levels of chemokines, resulting in exaggerated activation of the transcriptional nuclear factor (NF)-kappaB in airway epithelial cells. The present study was undertaken to evaluate the effects of anti-inflammatory cytokine interleukin-10 (IL-10) on NaCl-induced chemokine IL-8 and regulated on activation normal T cell expressed and secreted (RANTES) expression through the NF-kappaB signaling in primary deltaF508 CF and non-CF (control) human bronchial epithelial cells. Exposure of CF and non-CF bronchial epithelial cells to hypertonic (170 mmol/L NaCl) milieu compared to isotonic (115 mmol/L NaCl) and hypotonic (85 mmol/L NaCl) milieu caused a significant, NaCl-dependent increase in IL-8 and RANTES gene expression and protein production. Compared to non-CF cells, CF bronchial epithelial cells were characterized by a higher susceptibility to produce elevated IL-8 and RANTES production in an hypertonic NaCl milieu in response to IL-1beta activation. Treatment with IL-10 suppressed IL-8 and RANTES gene expression in both non-CF and CF bronchial epithelial cells was associated with a reduced expression of I(k)B (IKK) alpha/beta kinases, particularly for IKKalpha which is greater expressed in CF bronchial epithelial cells, and resulting in reduced NF-kappaB activation. These findings suggest that IL-10 might have anti-inflammatory benefits in airways of CF patients.