Inhibition of Toll-like receptor 2-mediated interleukin-8 production in Cystic Fibrosis airway epithelial cells via the alpha7-nicotinic acetylcholine receptor.
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.
Greene
Catherine M
CM
Department of Medicine, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. cmgreene@rcsi.ie
Ramsay
Hugh
H
Wells
Robert J
RJ
O'Neill
Shane J
SJ
McElvaney
Noel G
NG
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
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