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Position: Home > issue > May 28, 2021 Volume 2, Issue 2
Nicotine and its metabolite cotinine target MD2 and inhibit TLR4 signaling
Category: Report
Author: 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

2.jpg

Graphical abstract


Nicotine is the principal alkaloid of tobacco often manufactured into cigarettes and belongs to a highly addictive class of drugs. Nicotine attenuates the neuroinflammation induced by microglial activation. However, the molecular target(s) underlying anti-inflammatory action of nicotine has not been fully understood. Considering the psychoactive substances morphine, cocaine, and methamphetamine act as xenobiotic-associated molecular patterns and can be specifically sensed by the innate immune receptor Toll-like receptor 4 (TLR4), here we sought to delineate whether nicotine and/or its metabolite cotinine may be recognized by the innate immune system via myeloid differentiation protein 2 (MD2), an accessory protein of TLR4 that is responsible for ligand recognition.





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