烟碱激动剂
乙酰胆碱
胆碱能的
尼古丁
烟碱乙酰胆碱受体
医学
HMGB1
兴奋剂
麦加明
乙酰胆碱受体
败血症
烟碱拮抗剂
药理学
化学
肿瘤坏死因子α
受体
内科学
作者
Hong Wang,Hong Liao,Mahendar Ochani,Marilou Justiniani,Xinchun Lin,Lihong Yang,Yousef Al‐Abed,Haichao Wang,Christine N. Metz,Edmund J. Miller,Kevin J. Tracey,Luis Ulloa
出处
期刊:Nature Medicine
[Springer Nature]
日期:2004-10-24
卷期号:10 (11): 1216-1221
被引量:996
摘要
Physiological anti-inflammatory mechanisms can potentially be exploited for the treatment of inflammatory disorders. Here we report that the neurotransmitter acetylcholine inhibits HMGB1 release from human macrophages by signaling through a nicotinic acetylcholine receptor. Nicotine, a selective cholinergic agonist, is more efficient than acetylcholine and inhibits HMGB1 release induced by either endotoxin or tumor necrosis factor-alpha (TNF-alpha). Nicotinic stimulation prevents activation of the NF-kappaB pathway and inhibits HMGB1 secretion through a specific 'nicotinic anti-inflammatory pathway' that requires the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). In vivo, treatment with nicotine attenuates serum HMGB1 levels and improves survival in experimental models of sepsis, even when treatment is started after the onset of the disease. These results reveal acetylcholine as the first known physiological inhibitor of HMGB1 release from human macrophages and suggest that selective nicotinic agonists for the alpha7nAChR might have therapeutic potential for the treatment of sepsis.
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