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

Research output: Contribution to journalArticle

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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 - Jul 18 2005

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Neuropeptides
Mast Cells
Inflammation
Cell Degranulation
neuromedin U
Freund's Adjuvant
Neutrophil Infiltration
G-Protein-Coupled Receptors
Vasodilation
Gastrointestinal Tract
Monocytes
Edema
Central Nervous System

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells. / Moriyama, Maiko; Sato, Takahiro; Inoue, Hiromasa; Fukuyama, Satoru; Teranishi, Hitoshi; Kangawa, Kenji; Kano, Tatsuhiko; Yoshimura, Akihiko; Kojima, Masayasu.

In: Journal of Experimental Medicine, Vol. 202, No. 2, 18.07.2005, p. 217-224.

Research output: Contribution to journalArticle

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, vol. 202, no. 2, pp. 217-224. https://doi.org/10.1084/jem.20050248
Moriyama, Maiko ; Sato, Takahiro ; Inoue, Hiromasa ; Fukuyama, Satoru ; Teranishi, Hitoshi ; Kangawa, Kenji ; Kano, Tatsuhiko ; Yoshimura, Akihiko ; Kojima, Masayasu. / The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells. In: Journal of Experimental Medicine. 2005 ; Vol. 202, No. 2. pp. 217-224.
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