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Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.

Publication ,  Journal Article
Wang, H; Liao, H; Ochani, M; Justiniani, M; Lin, X; Yang, L; Al-Abed, Y; Wang, H; Metz, C; Miller, EJ; Tracey, KJ; Ulloa, L
Published in: Nature medicine
November 2004

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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Published In

Nature medicine

DOI

EISSN

1546-170X

ISSN

1078-8956

Publication Date

November 2004

Volume

10

Issue

11

Start / End Page

1216 / 1221

Related Subject Headings

  • alpha7 Nicotinic Acetylcholine Receptor
  • Signal Transduction
  • Sepsis
  • Receptors, Nicotinic
  • Oligonucleotides
  • Nicotine
  • Neuroimmunomodulation
  • Mice
  • Macrophages
  • Lipopolysaccharides
 

Citation

APA
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Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., … Ulloa, L. (2004). Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nature Medicine, 10(11), 1216–1221. https://doi.org/10.1038/nm1124
Wang, Hong, Hong Liao, Mahendar Ochani, Marilou Justiniani, Xinchun Lin, Lihong Yang, Yousef Al-Abed, et al. “Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.Nature Medicine 10, no. 11 (November 2004): 1216–21. https://doi.org/10.1038/nm1124.
Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, et al. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nature medicine. 2004 Nov;10(11):1216–21.
Wang, Hong, et al. “Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.Nature Medicine, vol. 10, no. 11, Nov. 2004, pp. 1216–21. Epmc, doi:10.1038/nm1124.
Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Metz C, Miller EJ, Tracey KJ, Ulloa L. Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nature medicine. 2004 Nov;10(11):1216–1221.

Published In

Nature medicine

DOI

EISSN

1546-170X

ISSN

1078-8956

Publication Date

November 2004

Volume

10

Issue

11

Start / End Page

1216 / 1221

Related Subject Headings

  • alpha7 Nicotinic Acetylcholine Receptor
  • Signal Transduction
  • Sepsis
  • Receptors, Nicotinic
  • Oligonucleotides
  • Nicotine
  • Neuroimmunomodulation
  • Mice
  • Macrophages
  • Lipopolysaccharides