title: Cigarette smoke increases Toll-like receptor 4 and modifies lipopolysaccharide-mediated responses in airway epithelial cells.
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 Toll-like 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-kappaB (NF-kappaB) 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-kappaB and ERK1/2 activation. The combined exposure of 16-HBE to CSE and LPS was associated with ERK activation rather than NF-kappaB 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.
authors.affiliation: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy. pace@ibim.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Liboria
authors.initials: L
authors.lastname: Siena
authors.forename: Mario
authors.initials: M
authors.lastname: Melis
authors.forename: Angela M
authors.initials: AM
authors.lastname: Montalbano
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
authors.forename: Maria R
authors.initials: MR
authors.lastname: Bonsignore
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bonsignore
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D001980:Bronchi / Q000276:immunology*; D002461:Cell Line, Transformed; D054357:Chemokine CXCL10 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D012906:Smoke; D014026:Nicotiana / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D054357:Chemokine CXCL10; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012906:Smoke; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3