Journal
SHOCK
Volume 26, Issue 4, Pages 358-364Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.shk.0000228168.86845.60
Keywords
lipopolysaccharide; monocyte; nicotine; nicotinic acetylcholine receptor alpha 7 subunit; CD14; toll-like receptor 4
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The lipopolysaccharide (LPS)-receptor complex, CD14/toll-like receptor 4, is known to play a role in the immune responses during sepsis. Excessive inflammation and tumor necrosis factor (TNF)-alpha synthesis have been reported to cause morbidity and mortality in endotoxemia and sepsis. Cell-to-cell interaction through the engagement between intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and their ligands on T cells has been suggested to play a role in the inflammatory response such as TNF-alpha and interleukin 10 production. Nicotine, with the stimulation of the nicotinic acetylcholine receptor alpha 7 subunit (alpha 7-nAChR), has now become the focus of attention because of its anti-inflammatory effects. However, little is known about the mechanism of the inhibitory effects induced by nicotine on the LPS-induced immune responses. In the present study, we found that nicotine suppressed the expression of CD14, toll-like receptor 4, intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and the production of TNF-alpha, but not interleukin 10, in human peripheral blood mononuclear cells in the presence of LPS. The actions of nicotine were reversed by a nonselective and a selective alpha 7-nAChR antagonist, mecamylamine and a-bungarotoxin, respectively. Therefore, nicotine might inhibit the LPS receptor complex expression via alpha 7-nAChR, thus leading to a decrease in the adhesion molecule expression and TNF-alpha production. Moreover, we demonstrated that a nuclear factor-kappa B and a p38 mitogen-activated protein kinase inhibitor mimicked the actions of nicotine in the presence of LPS. These results suggested that the nuclear factor-kappa B and p38 mitogen-activated protein kinase might be involved in the actions of nicotine.
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