Modulation of CXCL-8 production through the inflammasome signaling by human bronchial epithelial cells (16HBE14O)

Chronic obstructive pulmonary disease (COPD) is a major health problem and cigarette smoke is the main risk factor for the development of COPD. Exposure to cigarette smoke activates inflammatory cells for production of CXCL8. The Inflammasome is a multiprotein complex consisting of molecules and promotes the maturation of inflammatory reactions. The contribution of of IL-1b signaling in induction of CXCL8 has been reported. The epithelium is a barrier to the entry of pathogens, and as a dynamic system for host response, the epithelium can produce natural antimicrobial factors and release pro-inflammatory cytokines. Therefore, it is thought that the airway epithelium plays a role in modulating innate immunity. Recently, we have showed that cigarette smoke extracts (CSE) induces the production of CXCL8 via TLR9 and ATP pathways. In this study we extend the effects of CSE on the regulation of CXCL8 release by human bronchial epithelial cells (HBE-14o) via inflammasome signaling.In this study we investigated the role of inflammasome signaling in HBE-14o cells.We found that HBE-14o cells expressed surface expression of TLR9 which is modulated by CSE. Besides, CSE induced the release of CXCL-8 via inflammasome/caspase-1 signaling which is suppressed by pharmacologic inhibitors. Moreover, CSE activates NALP3 molecule which is demonstrated by Western blotting. In conclusion, we have shown that CS modulates the expression and production of CXCL8 by involvement of TLRs/inflammasome signal transduction and modulation these pathways might be consider for controling pathogenesis of COPD.