Cigarette smoke increases TLR4 and modifies LPS mediated responses in airway epithelial cells.

Airway epithelium is emerging as a regulator of innate immune responsesto a variety of insults including cigarette smoke. The main goal of thisstudy was to explore the effects of cigarette smoke extracts (CSE) on Tolllikereceptor (TLR) expression and activation in a human bronchial epithelialcell line (16-HBE). The CSE increased the expression of TLR4 andthe lipopolysaccharide (LPS) binding, the nuclear factor-jB (NF-jB) activation,the release of interleukin-8 (IL-8) and the chemotactic activitytoward neutrophils. It did not induce TLR2 expression or extracellularsignal-regulated signal kinase 1/2 (ERK1/2) activation. The LPS increasedthe expression of TLR4 and induced both NF-jB and ERK1/2 activation.The combined exposure of 16-HBE to CSE and LPS was associated withERK activation rather than NF-jB activation and with a further increaseof IL-8 release and of chemotactic activity toward neutrophils. Furthermore,CSE decreased the constitutive interferon-inducible protein-10(IP-10) release and counteracted the effect of LPS in inducing both theIP-10 release and the chemotactic activity toward lymphocytes. In conclusion,cigarette smoke, by altering the expression and the activation ofTLR4 via the preferential release of IL-8, may contribute to the accumulationof neutrophils within the airways of smokers.