Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I‐κB phosphorylation and nuclear factor‐κB transcriptional activity through nicotinic acetylcholine receptor α7

Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis factor (TNF)‐α, prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)‐1α and MIP‐1α, play a critical role in the progression of immunological disorders including rheumatoid arthritis, Behçet’s disease and Crohn’s disease. In addition, the nicotinic acetylcholine receptor‐α7 (α7nAChR) subunit is an essential regulator of inflammation. In this study, we evaluated the expression of the α7nAChR subunit on human peripheral monocytes and the effect of nicotine on the production of these proinflammatory mediators by activated monocytes. Fluorescein isothiocyanate (FITC)‐labelled α‐bungarotoxin demonstrated the cell surface expression of the α7nAchR subunit. Pretreatment with low‐dose nicotine caused inhibition of TNF‐α, PGE2, MIP‐1α and MIP‐1α production, and mRNA expression of TNF‐α, MIP‐1α and MIP‐1α and COX‐2 in lipopolysaccharide (LPS)‐activated monocytes. These suppressive effects of nicotine were caused at the transcriptional level and were mediated through α7nAChR. Nicotine suppressed the phosphorylation of I‐κB, and then inhibited the transcriptional activity of nuclear factor‐κB. These immunosuppressive effects of nicotine may contribute to the regulation of some immune diseases.

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