Cigarette smoke increases TLR4 and modifies LPS mediated responses in airway epithelial cells.
- Authors: Pace, E; Ferraro, M; Siena, L; Melis, M; Montalbano, A; Johnson, M; Bonsignore, MR; Bonsignore, G; Gjomarkaj, M
- Publication year: 2008
- Type: Articolo in rivista (Articolo in rivista)
- Key words: airway epithelial cell; cigarette smoke; Toll-like receptors
- OA Link: http://hdl.handle.net/10447/45986
Abstract
Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke. The main goal of this study was to explore the effects of cigarette smoke extracts (CSE) on Tolllike receptor (TLR) expression and activation in a human bronchial epithelial cell line (16-HBE). The CSE increased the expression of TLR4 and the lipopolysaccharide (LPS) binding, the nuclear factor-jB (NF-jB) activation, the release of interleukin-8 (IL-8) and the chemotactic activity toward neutrophils. It did not induce TLR2 expression or extracellular signal-regulated signal kinase 1/2 (ERK1/2) activation. The LPS increased the expression of TLR4 and induced both NF-jB and ERK1/2 activation. The combined exposure of 16-HBE to CSE and LPS was associated with ERK activation rather than NF-jB activation and with a further increase of 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 the IP-10 release and the chemotactic activity toward lymphocytes. In conclusion, cigarette smoke, by altering the expression and the activation of TLR4 via the preferential release of IL-8, may contribute to the accumulation of neutrophils within the airways of smokers.