Cigarette smoke modulates release of CXCL8 through the inflammasome signaling in human bronchial epithelial cells (16HBE14o)

Chronic obstructive pulmonary disease (COPD) is a major healthproblem and cigarette smoke (CS) is the main risk factor forthe development of COPD. Exposure to cigarette smoke activatesinflammatory cells for production of CXCL8 with accompanyingdamage to the lung epithelium and recruitment of macrophagesand neutrophils. The Inflammasome is a multiprotein complexconsisting of caspase-1, and NALP molecules and promotes thematuration of inflammatory cytokines such as interleukin 1-βand IL-18. The role of IL-1β in induction of CXCL8 hasbeen reported. The epithelium is a barrier to the entry of pathogens,and as a dynamic system for host response. The epithelium canproduce natural antimicrobial factors and release pro-inflammatorycytokines. Therefore it is thought that the airway epitheliumplays a role in modulating innate immunity. In this study westudied the effects of CS on the regulation of CXCL8 releasevia inflammasome signaling by HBE-14o cell lines. We found thatin HBE-14o preincubation with anti-caspase-1 (Z-VAD-FMK) suppressedthe release of CXCL8 induced by CSE. Moreover, CSE induced maturationof IL-1β (17 KD) and activates NALP3 molecules which isdemonstrated by Western blotting. In conclusion this study indicatesthat inflammasome signaling may directly or indirectly promotethe production of CXCL8 by human bronchial epithelial cells.