Cigarette smoke induces CXCL8 production by human neutrophils via activation of TLR9 receptor.
Chronic obstructive pulmonary disease (COPD) is a major health problem and cigarette smoke is the main risk factor for the development of COPD. The characteristic changes in airway morphology, inflammatory cell infiltration and mediator expression in COPD may result from direct effects of cigarette smoke on airway cells. Toll-like receptors (TLRs) are key elements in pathogen recognition by the host immune system. Although TLRs have been intensely studied in innate immunity and infection, their critical role in noninfectious challenges has only recently emerged. Here we investigate whether cigarette smoke induces TLR9 signalling in human neutrophils. Human neutrophils were isolated from buffy coat and exposed to cigarette smoke extract. The production of CXC chemokine ligand (CXCL)8 was measured as a functional readout and the role of TLR9 signalling was investigated. Cigarette smoke extract induced CXCL8 release via TLR9 activation in neutrophils, which was confirmed in TLR9 stably transfected human embryonic kidney 293 cells. Moreover, cigarette smoke extract upregulated the expression of TLR9 and the upregulated expression was suppressed by N-acetylcysteine. TLR9 mediates cigarette smoke-induced release of CXCL8 and this may contribute to the accumulation of neutrophils and inflammation within the airways of smokers.
Division of Pharmacology and Pathophysiology Utrecht Institute for Pharmaceutical Sciences Faculty of Sciences, Utrecht University, PO BOX 80082, 3508 TB Utrecht, The Netherlands. emortaz@gmail.com
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Mortaz
I M
IM
Adcock
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Ito
A D
AD
Kraneveld
F P
FP
Nijkamp
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Folkerts
D057809:HEK293 Cells; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D011014:Pneumonia / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000276:immunology; D012907:Smoking / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D009569:Nitric Oxide