Cited by 3,228Vagus Nerve Stimulation ResearchNicotinic Acetylcholine Receptors StudyNeuroinflammation and Neurodegeneration Mechanisms

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Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation

Wang, Hong, Yu, Man, Ochani, Mahendar, Amella, Carol Ann, Tanovic, Mahira, Susarla, Seenu, Li, Jian Hua, Wang, Haichao, Yang, Huan, Ulloa, Luis, Al-Abed, Yousef, Czura, Christopher J., Tracey, Kevin J.·2003·Nature

DOI 10.1038/nature01339

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Abstract

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.

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Authors: Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., Al-Abed, Y., Czura, C. J., & Tracey, K. J.
Corresponding author: Tracey, Kevin J.
ORCID: Wang, Hong
Yu, Man
Amella, Carol Ann
Wang, Haichao
Yang, Huan
Ulloa, Luis
Czura, Christopher J.
Tracey, Kevin J.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2002-12-22
Volume: 421
Issue: 6921
Pages: 384-388
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature01339
OpenAlex: W2073295417
Cited by: 3,228
References: 26
Citations by year: 2026: 142 · 2025: 128 · 2024: 181 · 2023: 141 · 2022: 180 · 2021: 203 · 2020: 181 · 2019: 169 · 2018: 154 · 2017: 164 · 2016: 146 · 2015: 142 · 2014: 160 · 2013: 133 · 2012: 127
FWCI: 36.13
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: cholinergic anti-inflammatory pathway, vagus nerve, acetylcholine, inflammation regulation, innate immune response, cytokine production
MeSH terms: Acetylcholine, Aging, Animals, Bungarotoxins, Cells, Cultured, Electric Stimulation, Female, Humans, Inflammation, Male, Mice, Inbred C57BL, Nicotine, Receptors, Nicotinic, RNA, Messenger, Tumor Necrosis Factor-alpha, Vagus Nerve, Macrophages, Peritoneal, Mice, Knockout, Endotoxemia, Protein Subunits, Mice, alpha7 Nicotinic Acetylcholine Receptor

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Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation

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