The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia

Maiko Moriyama, Satoru Fukuyama, Hiromasa Inoue, Takafumi Matsumoto, Takahiro Sato, Kentaro Tanaka, Ichiko Kinjyo, Tatsuhiko Kano, Akihiko Yoshimura, Masayasu Kojima

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Neuromedin U (NMU) is a neuropeptide expressed not only in the central nervous system but also in various organs, including the gastrointestinal tract and lungs. NMU interacts with two G protein-coupled receptors, NMU-R1 and NMU-R2. Although NMU-R2 is expressed in a specific region of the brain, NMU-R1 is expressed in various peripheral tissues, including immune and hematopoietic cells. Our recent study demonstrated an important role of NMU in mast cell-mediated inflammation. In this study, we showed that airway eosinophilia was reduced in NMU-deficient mice in an allergen-induced asthma model. There were no differences in the antigen-induced Th2 responses between wild-type and NMU knockout mice. NMU-R1 was highly expressed in the eosinophil cell line, and NMU directly induced Ca2+ mobilization and extracellular/signal- regulated kinase phosphorylation. NMU also induced cell adhesion to components of the extracellular matrix (fibronectin and collagen type I), and chemotaxis in vitro. Furthermore, NMU-R1 was also expressed in human peripheral blood eosinophils, and NMU induced cell adhesion in a dose-dependent manner. These data indicate that NMU promotes eosinophil infiltration into inflammatory sites by directly activating eosinophils. Our study suggests that NMU receptor antagonists could be novel targets for pharmacological inhibition of allergic inflammatory diseases, including asthma.

Original languageEnglish
Pages (from-to)L971-L977
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume290
Issue number5
DOIs
Publication statusPublished - May 1 2006

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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