title: Therapeutic effects of novel sphingosine-1-phosphate receptor agonist W-061 in murine DSS colitis.
abstract: Although IL-17 is a pro-inflammatory cytokine reportedly involved in various autoimmune inflammatory disorders, its role remains unclear in murine models of colitis. Acute colitis was induced by 2.5% dextran sodium sulfate (DSS) treatment for 5 days. A novel sphingosine-1-phosphate receptor agonist W-061, a prototype of ONO-4641, was orally administered daily, and histopathological analysis was performed on the colon. The number of lymphocytes and their cytokine production were also evaluated in spleen, mesenteric lymph node, Peyer's patch and lamina propria of the colon. Daily administration of W-061 resulted in improvement of DSS-induced colitis, and significantly reduced the number of CD4+ T cells in the colonic lamina propria. Numbers of both Th17 and Th1 cells were reduced by W-061 treatment. W-061, however, had no influence on the number of Treg cells in lamina propria. Thus, Th17 and Th1 cells in lamina propria were thought to be the key subsets in the pathogenesis of DSS-induced colitis. In conclusion, W-061 may be a novel therapeutic strategy to ameliorate acute aggravation of inflammatory bowel diseases.
authors.affiliation: Department of Complementary Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Sanada
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kai
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hagiya
authors.forename: Haruto
authors.initials: H
authors.lastname: Kurata
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Mizuno
authors.forename: Etsuko
authors.initials: E
authors.lastname: Uejima
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ito
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D002465:Cell Movement / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D016264:Dextran Sulfate / Q000009:adverse effects*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013379:Substrate Specificity; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D049349:Receptors, Lysosphingolipid; D016264:Dextran Sulfate