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Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation

Author

Listed:
  • Hong Wang

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Man Yu

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Mahendar Ochani

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Carol Ann Amella

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Mahira Tanovic

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Seenu Susarla

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Jian Hua Li

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Haichao Wang

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Huan Yang

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Luis Ulloa

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Yousef Al-Abed

    (Laboratory of Medicinal Chemistry, North Shore Long Island Jewish Research Institute)

  • Christopher J. Czura

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

  • Kevin J. Tracey

    (Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute)

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 disease1,2,3,4. 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 responses5,6,7. This physiological mechanism, termed the ‘cholinergic anti-inflammatory pathway’5 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 α7 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 α7-deficient mice. Thus, the nicotinic acetylcholine receptor α7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.

Suggested Citation

  • Hong Wang & Man Yu & Mahendar Ochani & Carol Ann Amella & Mahira Tanovic & Seenu Susarla & Jian Hua Li & Haichao Wang & Huan Yang & Luis Ulloa & Yousef Al-Abed & Christopher J. Czura & Kevin J. Tracey, 2003. "Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation," Nature, Nature, vol. 421(6921), pages 384-388, January.
    • Handle: RePEc:nat:nature:v:421:y:2003:i:6921:d:10.1038_nature01339
    DOI: 10.1038/nature01339
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    Cited by:

    1. Koji Hosomi & Mayu Saito & Jonguk Park & Haruka Murakami & Naoko Shibata & Masahiro Ando & Takahiro Nagatake & Kana Konishi & Harumi Ohno & Kumpei Tanisawa & Attayeb Mohsen & Yi-An Chen & Hitoshi Kawa, 2022. "Oral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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