Nicotine attenuates concanavalin A-induced liver injury in mice by regulating the α7-nicotinic acetylcholine receptor in Kupffer cells.

Nicotine, a potent parasympathomimetic alkaloid, manifests anti-inflammatory properties by activating nicotinic acetylcholine receptors (nAChRs). In this study, we evaluated the effects of nicotine on concanavalin A (ConA)-induced autoimmune hepatitis. Nicotine (0.5 and 1 mg/kg) was intraperitoneally administered to BALB/c mice and mice were intravenously injected with ConA (15 mg/kg) to induce hepatitis. The results showed that nicotine treatment ameliorated pathological lesions in livers and significantly suppressed the expression of pro-inflammatory cytokines in the livers. Such effects were mediated by inhibiting the nuclear factor-kappa B (NF-κB) signaling in livers. Interestingly, nicotine inhibited the ConA-induced inflammatory response in primary cultured Kupffer cells (KCs) but did not alter the proliferation of splenocytes. The protective effects of nicotine against ConA-induced hepatitis were abolished in KC-depleted mice, indicating the requirement of KCs in this process. Additionally, the expression of α7-nAChR on KCs was dramatically increased by nicotine treatment, and the protective effects of nicotine on ConA-induced liver injury were significantly suppressed by treatment with methyllycaconitine (MLA), a specific α7-nAChR antagonist. Consistently, in primary cultured KCs, the activation of NF-κB signaling was also regulated by nicotine treatment. This study suggests that nicotine increases α7-nAChR-mediated cholinergic activity in KCs resulting in decrease of ConA-induced autoimmune hepatitis through inhibiting NF-κB signaling.