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Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.
Nat Med. 2004 Nov; 10(11):1216-21.NMed

Abstract

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.

Authors+Show Affiliations

The Center for Immunology and Inflammation, North Shore-LIJ Research Institute, North Shore University Hospital, 350 Community Drive, Manhasset, New York 11030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15502843

Citation

Wang, Hong, et al. "Cholinergic Agonists Inhibit HMGB1 Release and Improve Survival in Experimental Sepsis." Nature Medicine, vol. 10, no. 11, 2004, pp. 1216-21.
Wang H, Liao H, Ochani M, et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med. 2004;10(11):1216-21.
Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., Al-Abed, Y., Wang, H., Metz, C., Miller, E. J., Tracey, K. J., & Ulloa, L. (2004). Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nature Medicine, 10(11), 1216-21.
Wang H, et al. Cholinergic Agonists Inhibit HMGB1 Release and Improve Survival in Experimental Sepsis. Nat Med. 2004;10(11):1216-21. PubMed PMID: 15502843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. AU - Wang,Hong, AU - Liao,Hong, AU - Ochani,Mahendar, AU - Justiniani,Marilou, AU - Lin,Xinchun, AU - Yang,Lihong, AU - Al-Abed,Yousef, AU - Wang,Haichao, AU - Metz,Christine, AU - Miller,Edmund J, AU - Tracey,Kevin J, AU - Ulloa,Luis, Y1 - 2004/10/24/ PY - 2004/06/21/received PY - 2004/09/28/accepted PY - 2004/10/27/pubmed PY - 2005/2/5/medline PY - 2004/10/27/entrez SP - 1216 EP - 21 JF - Nature medicine JO - Nat Med VL - 10 IS - 11 N2 - 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. SN - 1078-8956 UR - https://www.unboundmedicine.com/medline/citation/15502843/Cholinergic_agonists_inhibit_HMGB1_release_and_improve_survival_in_experimental_sepsis_ L2 - https://doi.org/10.1038/nm1124 DB - PRIME DP - Unbound Medicine ER -