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

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/W(v) 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 WBB6F(1)-W/W(v) 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.

• Authors: Maiko Moriyama, Takahiro Sato, Hiromasa Inoue, Satoru Fukuyama, Hitoshi Teranishi, Kenji Kangawa, Tatsuhiko Kano, Akihiko Yoshimura, Masayasu Kojima
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 202 Issue 2 Pg. 217-24 (Jul 18 2005) ISSN: 0022-1007 [Print] United States
• PMID: 16009716 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Neuropeptides
• Receptors, Neurotransmitter
• neuromedin U receptor
• neuromedin U
• Freund's Adjuvant

Topics

• Animals
• Calcium Signaling (drug effects, genetics)
• Cell Degranulation (genetics, physiology)
• Central Nervous System (metabolism)
• Edema (genetics, metabolism, pathology)
• Freund's Adjuvant (administration & dosage)
• Inflammation (genetics, metabolism, pathology)
• Injections, Subcutaneous
• Lymphocytes (metabolism)
• Mast Cells (metabolism, pathology)
• Membrane Proteins (metabolism)
• Mice
• Mice, Knockout
• Monocytes (metabolism)
• Neuropeptides (administration & dosage, genetics, metabolism)
• Neutrophil Infiltration (drug effects, genetics)
• Receptors, Neurotransmitter (metabolism)
• Skin (metabolism, pathology)