title: Epidermal Neuromedin U Attenuates IgE-Mediated Allergic Skin Inflammation.
abstract: Although keratinocyte-derived neuropeptide neuromedin U (NMU) mediates the proinflammatory effects of innate-type mast cell activation, no information is available on the physiological roles. Here, to investigate the effects of NMU on IgE-mediated allergic skin inflammation, we determined whether IgE-mediated inflammation associated with severe scratching was induced in Nmu-/- mice administered repeated hapten applications to the ear or footpad. Dry skin was induced by targeted deletion of Nmu. Mice administered repeated hapten application developed IgE-mediated allergic inflammation characterized by severe scratching and increased serum IgE levels only when the ear, and not the footpad, was subjected to scratching, indicating that depletion of NMU from the epidermis alone does not drive such allergic inflammation. Thus, the susceptibility of Nmu-/- mice to allergic inflammation depends primarily on scratching dry skin. Further, allergic skin inflammation mediated by FcεRI cross-linking in Nmu-/-mice was inhibited by prior injection of NMU. These results indicate that NMU plays an important physiological role as a negative regulator during the late stage of IgE-mediated allergic skin inflammation.
authors.affiliation: Department of Dermatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Mizukawa
authors.affiliation: Department of Dermatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department of Dermatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kudo
authors.affiliation: Department of Dermatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shiohara
mesh_terms: D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006241:Haptens / Q000633:toxicity; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D006241:Haptens; D009479:Neuropeptides; C056900:neuromedin U; D007073:Immunoglobulin E