Nicotinic acetylcholine receptor alpha 7 subunit is an essential regulator of inflammation Export

@article{wang03nicotinic, abstract = {1: Nature. 2003 Jan 23;421(6921):384-8. Epub 2002 Dec 22. Links Comment in: Nature. 2003 Jan 23;421(6921):328-9. Scand J Rheumatol. 2003;32(4):256. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. 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. Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute, 350 Community Drive, Manhasset, New York 11030, USA. 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.}, author = {Wang, H. and Yu, M. and Ochani, M. and Amella, C. A. and Tanovic, M. and Susarla, S. and Li, J. H. and Wang, H. and Yang, H. and Ulloa, L. and Others}, citeulike-article-id = {3298371}, journal = {Nature}, keywords = {vagus}, pages = {384--388}, posted-at = {2008-09-20 13:19:49}, priority = {2}, title = {Nicotinic acetylcholine receptor alpha 7 subunit is an essential regulator of inflammation}, volume = {421}, year = {2003} }

TY - JOUR ID - wang03nicotinic L3 - citeulike-article-id:3298371 N2 - 1: Nature. 2003 Jan 23;421(6921):384-8. Epub 2002 Dec 22. Links Comment in: Nature. 2003 Jan 23;421(6921):328-9. Scand J Rheumatol. 2003;32(4):256. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. 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. Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute, 350 Community Drive, Manhasset, New York 11030, USA. 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. JF - Nature EP - 388 TI - Nicotinic acetylcholine receptor alpha 7 subunit is an essential regulator of inflammation VL - 421 SP - 384 KW - vagus AU - Wang, H AU - Yu, M AU - Ochani, M AU - Amella, CA AU - Tanovic, M AU - Susarla, S AU - Li, JH AU - Wang, H AU - Yang, H AU - Ulloa, L AU - Others PY - 2003/// ER -