Nicotine and its metabolite cotinine target MD2 and inhibit TLR4 signaling
Hongyuan Li, Yinghua Peng, Cong Lin, Xiaozheng Zhang, Tianshu Zhang, Yibo Wang, Yuanpeng Li, Siru Wu, Hongshuang Wang, Mark R. Hutchinson, Linda R. Watkins, Xiaohui Wang
Abstract
simulations. In keeping with targeting MD2, both nicotine and cotinine inhibited LPS-induced production of nitric oxide and tumor necrosis factor alpha (TNF-α) and blocked microglial activation. Neither a pan nicotinic acetylcholine receptor (nAChR) inhibitor nor RNAi for nAChRs abolished the suppressive effect of nicotine- and cotinine-induced neuroinflammation. These data indicate that TLR4 inhibition by nicotine and cotinine at the concentrations tested in BV-2 cells is independent of classic neuronal nAChRs and validate that MD2 is a direct target of nicotine and cotinine in the inhibition of innate immunity.