title: A sphingosine 1-phosphate receptor agonist ameliorates animal model of vasculitis.
abstract: OBJECTIVE
  Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to cell surface receptors (S1P1-5). In this study, we examined the effect of S1P1agonist, ONO-W061, on murine Candida albicans water-soluble fraction (CAWS)-induced vasculitis.
  
  
  METHODS
  Mice were administered ONO-W061, and the number of peripheral blood cells was counted. Vasculitis was induced by an intraperitoneal injection of CAWS. Expression of S1P receptors and CXCL1 was analyzed by quantitative RT-PCR. ONO-W061 was orally administered, and vasculitis was evaluated histologically. Number of neutrophils, macrophages and T cells in the vasculitis tissue was counted using flow cytometry. Production of chemokines from S1P-stimulated human umbilical vein endothelial cells (HUVECs) was measured by ELISA.
  
  
  RESULTS
  Number of peripheral blood lymphocytes was decreased by ONO-W061. Expression of CXCL1 and S1P1was enhanced in CAWS-induced vasculitis tissue. Vasculitis score, CXCL1 and number of neutrophils in the vasculitis tissue were lower in ONO-W061-treated mice. Treatment of HUVECs with S1P upregulated the production of CXCL1 and IL-8 in vitro, and this was inhibited by ONO-W061.
  
  
  CONCLUSIONS
  ONO-W061 significantly improved CAWS-induced vasculitis. This effect may be partly exerted through the inhibited production of chemokines by endothelial cells, which in turn could induce neutrophil recruitment into inflamed vessels.
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.|Department of Dermatology, Tokyo Medical University, 6-7-1, Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.|Center for Immunology and Inflammatory Disease, Department of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, CNY149-8 13th St, Boston, MA, 02129, USA.
authors.forename: Chie
authors.initials: C
authors.lastname: Miyabe
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.|Center for Immunology and Inflammatory Disease, Department of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, CNY149-8 13th St, Boston, MA, 02129, USA.
authors.forename: Yoshishige
authors.initials: Y
authors.lastname: Miyabe
authors.affiliation: Department of Biology and Pharmacology, Ono Pharmaceutical Co. Ltd, 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Komiya
authors.affiliation: Department of Biology and Pharmacology, Ono Pharmaceutical Co. Ltd, 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shioya
authors.affiliation: Department of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Science School of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Noriko N
authors.initials: NN
authors.lastname: Miura
authors.affiliation: Department of Pathology, Toho University, 2-17-6 Ohashi, Meguro, Tokyo, 153-8515, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Science School of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
authors.affiliation: Department of Dermatology, Tokyo Medical University, 6-7-1, Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
authors.affiliation: Center for Immunology and Inflammatory Disease, Department of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, CNY149-8 13th St, Boston, MA, 02129, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.affiliation: Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. toshihiro.nanki@med.toho-u.ac.jp.|Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan. toshihiro.nanki@med.toho-u.ac.jp.|Department of Clinical Research Medicine, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. toshihiro.nanki@med.toho-u.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nanki
mesh_terms: D000818:Animals; D002176:Candida albicans; D054360:Chemokine CXCL1 / Q000378:metabolism; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007958:Leukocyte Count; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D049349:Receptors, Lysosphingolipid / Q000819:agonists*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; D016209:Interleukin-8; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Chemokine; Sphingosine 1-phosphate; Sphingosine 1-phosphate receptor 1; Vasculitis