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

COPD is a chronic airway diseases associated with inflammation and cigarette smoking. Airway epithelial cells are the first cells that will be exposed to cigarette smoke and are able to release CXCL-8 and IL-1β. These cytokines are involved in the acute and chronic character of inflammatory processes in COPD. The aim of this study was to investigate whether Toll Like Receptors (TLRs) on human bronchial epithelial cells (HBE14o cells) were involved in cigarette smokeinduced cytokine production. The cigarette smokeinduced 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 HBE14o cells to TLR4 or TLR9 ligands resulted in the release of CXCL-8 and IL-1β. TLR4 and also TLR9 were present on the cell surface and the expression of both receptors decreased after cigarette smoke exposure. The molecular mechanism was further investigated. It was found that the purinergic P2X7 receptors and reactive oxygen species were involved. Interestingly, the inflammasome activator monosodium urate crystals (MSU) mimicked the release of CXCL-8 and IL-1β and the caspase1 inhibitor ZVADDCB suppressed the cigarette smokeinduced release of CXCL-8. In addition, cigarette smoke, CpGODN, LPS and MSU all increased the expression of caspase1 and IL-1β. In conclusion, cigarette smoke releases CXCL-8 from HBE14o cells via TLR4 and TLR9 and inflammasome activation. This signal transductions pathways may contribute to cigarette smoke related diseases such as COPD.