Submitted on August 10, 2005
Accepted on December 20, 2005
The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia
Maiko Moriyama1*, Satoru Fukuyama2, Hiromasa Inoue2, Takafumi Matsumoto2, Takahiro Sato3, Kentaro Tanaka4, Ichiko Kinjyo5, Tatsuhiko Kano6, Akihiko Yoshimura5, and Masayasu Kojima3
1 Department of Molecular Genetics, Institute of Life Sciences, Kurume University, Kurume, Fukuoka, Japan; Department of Anesthesiology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
2 Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan
3 Department of Molecular Genetics, Institute of Life Sciences, Kurume University, Kurume, Fukuoka, Japan
4 Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan; Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, Japan
5 Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, Japan
6 Department of Anesthesiology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
* To whom correspondence should be addressed. E-mail: moriyama{at}lsi.kurume-u.ac.jp.
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. While 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 knock-out mice. NMU-R1 was highly expressed in the eosinophil cell line, and NMU directly induced Ca2+ mobilization and ERK 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 a novel target for pharmacological inhibition of allergic inflammatory diseases including asthma.
