Regulation of the release of CXCL-8 from human bronchial epithelial cells via TLRs and induction of the inflammasome

Introduction: COPD is a chronic airway disease associated with inflammation and cigarette smoking. Airway epithelial cells are the first cells exposed to cigarette smoke and can release CXCL-8 and IL-1β. These cytokines are involved in acute and chronic inflammatory processes in COPD. The aim of this study was to investigate whether Toll Like Receptors (TLRs) on epithelial cells were involved in cigarette smoke-induced cytokine production. Materials, methods and results: Here we demonstrated that cigarette smoke induces the release of CXCL-8 and IL-1β from human bronchial epithelial cells (HBE-14o cells). Cigarette smoke-induced CXCL-8 production was inhibited by an antibody against TLR4 and by inhibitory ODN without CpGODN motif suggesting the involvement of TLR4 and TLR9. In addition, exposure of HBE-14o cells to TLR4 or TLR9 ligands resulted in the release of CXCL8 and IL1β. TLR4 and also TLR9 were present on the cell surface and the expression of both receptors decreased after cigarette smoke exposure. The molecular mechanism of the cigarette smoke-induced CXCL-8 production by the epithelial cells was further investigated. It was found that P2X7 receptors and reactive oxygen species were involved. Interestingly, the inflammasome activator monosodium urate crystals (MSU) induced the release of CXCL-8 and IL-1β and the caspase-1 inhibitor Z-VADDCB suppressed the cigarette smoke-induced release of CXCL-8. In addition, cigarette smoke, CpGODN, LPS and MSU all increased the expression of caspase- 1 and IL-1β. In conclusion, our results demonstrated that cigarette smoke releases CXCL-8 from HBE-14o cells via TLR4 and TLR9 and inflammasome activation. Conclusion: Therefore, inflammasome signaling in airway epithelial cells might play an important role in pathogenesis of diseases like COPD.