The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells

Maiko Moriyama, Takahiro Sato, Hiromasa Inoue, Satoru Fukuyama, Hitoshi Teranishi, Kenji Kangawa, Tatsuhiko Kano, Akihiko Yoshimura, Masayasu Kojima

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58 Citations (Scopus)

Abstract

Neuromedin U (NMU) is a neuropeptide that is expressed in the gastrointestinal tract and central nervous system. NMU interacts with two G protein-coupled receptors, NMU-R1 and NMU-R2. Whereas NMU-R2 localizes predominantly to nerve cells, NMU-R1 is expressed in peripheral tissues including lymphocytes and monocytes, suggesting a role of NMU in immunoregulation. However, the functions of NMU in peripheral tissues have not been clarified. In this study, using NMU-deficient mice, we first demonstrated that NMU plays an important role in mast cell-mediated inflammation. Complete Freund's adjuvant-induced mast cell degranulation as well as edema and neutrophil infiltration, which occurred weakly in mast cell-deficient WBB6F 1 - W/Wv mice, did not occur in NMU-deficient mice. Moreover, intraplantar injection of NMU into paws induced early inflammatory responses such as mast cell degranulation, vasodilation, and plasma extravasation in WT mice but not in WBB6F1 - W/Wv mice. NMU-R1 was highly expressed in primary mast cells, and NMU induced Ca 2+ mobilization and degranulation in peritoneal mast cells. These data indicate that NMU promotes mast cell-mediated inflammation; therefore, NMU receptor antagonists could be a novel target for pharmacological inhibition of mast cell-mediated inflammatory diseases.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalJournal of Experimental Medicine
Volume202
Issue number2
DOIs
Publication statusPublished - 2005 Jul 18
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Moriyama, M., Sato, T., Inoue, H., Fukuyama, S., Teranishi, H., Kangawa, K., Kano, T., Yoshimura, A., & Kojima, M. (2005). The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells. Journal of Experimental Medicine, 202(2), 217-224. https://doi.org/10.1084/jem.20050248