title: The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia.
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 Ca(2+) 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.
authors.affiliation: Department of Molecular Genetics, Institute of Life Sciences, Kurume University, 1-1 Hyakunen-kohen, Kurume, Fukuoka 839-0864, Japan. moriyama@lsi.kurume-u.ac.jp
authors.forename: Maiko
authors.initials: M
authors.lastname: Moriyama
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.forename: Takafumi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Ichiko
authors.initials: I
authors.lastname: Kinjyo
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kano
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kojima
mesh_terms: D000485:Allergens; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D020013:Calcium Signaling / Q000502:physiology; D002448:Cell Adhesion / Q000276:immunology / Q000502:physiology; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004804:Eosinophils / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000187:drug effects
chemical_list: D000485:Allergens; D008565:Membrane Proteins; D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U