Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.

Published

Journal Article

Excessive inflammation and tumour-necrosis factor (TNF) synthesis cause morbidity and mortality in diverse human diseases including endotoxaemia, sepsis, rheumatoid arthritis and inflammatory bowel disease. Highly conserved, endogenous mechanisms normally regulate the magnitude of innate immune responses and prevent excessive inflammation. The nervous system, through the vagus nerve, can inhibit significantly and rapidly the release of macrophage TNF, and attenuate systemic inflammatory responses. This physiological mechanism, termed the 'cholinergic anti-inflammatory pathway' has major implications in immunology and in therapeutics; however, the identity of the essential macrophage acetylcholine-mediated (cholinergic) receptor that responds to vagus nerve signals was previously unknown. Here we report that the nicotinic acetylcholine receptor alpha7 subunit is required for acetylcholine inhibition of macrophage TNF release. Electrical stimulation of the vagus nerve inhibits TNF synthesis in wild-type mice, but fails to inhibit TNF synthesis in alpha7-deficient mice. Thus, the nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.

Full Text

Duke Authors

Cited Authors

  • Wang, H; Yu, M; Ochani, M; Amella, CA; Tanovic, M; Susarla, S; Li, JH; Wang, H; Yang, H; Ulloa, L; Al-Abed, Y; Czura, CJ; Tracey, KJ

Published Date

  • January 23, 2003

Published In

Volume / Issue

  • 421 / 6921

Start / End Page

  • 384 - 388

PubMed ID

  • 12508119

Pubmed Central ID

  • 12508119

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature01339

Language

  • eng

Conference Location

  • England