title: Inhibition of Toll-like receptor 2-mediated interleukin-8 production in Cystic Fibrosis airway epithelial cells via the alpha7-nicotinic acetylcholine receptor.
abstract: Cystic Fibrosis (CF) is an inherited disorder characterised by chronic inflammation of the airways. The lung manifestations of CF include colonization with Pseudomonas aeruginosa and Staphylococcus aureus leading to neutrophil-dominated airway inflammation and tissue damage. Inflammation in the CF lung is initiated by microbial components which activate the innate immune response via Toll-like receptors (TLRs), increasing airway epithelial cell production of proinflammatory mediators such as the neutrophil chemokine interleukin-8 (IL-8). Thus modulation of TLR function represents a therapeutic approach for CF. Nicotine is a naturally occurring plant alkaloid. Although it is negatively associated with cigarette smoking and cardiovascular damage, nicotine also has anti-inflammatory properties. Here we investigate the inhibitory capacity of nicotine against TLR2- and TLR4-induced IL-8 production by CFTE29o- airway epithelial cells, determine the role of alpha7-nAChR (nicotinic acetylcholine receptor) in these events, and provide data to support the potential use of safe nicotine analogues as anti-inflammatories for CF.
authors.affiliation: Department of Medicine, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. cmgreene@rcsi.ie
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Greene
authors.forename: Hugh
authors.initials: H
authors.lastname: Ramsay
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wells
authors.forename: Shane J
authors.initials: SJ
authors.lastname: O'Neill
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003550:Cystic Fibrosis / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D047569:Laser Scanning Cytometry; D008070:Lipopolysaccharides / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism; D014132:Trachea / Q000166:cytology*; D015054:Zymosan / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D011978:Receptors, Nicotinic; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D015054:Zymosan