Chie Miyabe1,2,3, Yoshishige Miyabe1,3, Takaki Komiya4, Hiroki Shioya4, Noriko N Miura5, Kei Takahashi6, Naohito Ohno5, Ryoji Tsuboi2, Andrew D Luster3, Shinichi Kawai7, Nobuyuki Miyasaka1, Toshihiro Nanki8,9,10. 1. 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. 2. Department of Dermatology, Tokyo Medical University, 6-7-1, Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan. 3. 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. 4. Department of Biology and Pharmacology, Ono Pharmaceutical Co. Ltd, 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan. 5. Department of Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Science School of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. 6. Department of Pathology, Toho University, 2-17-6 Ohashi, Meguro, Tokyo, 153-8515, Japan. 7. Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan. 8. 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. 9. 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. 10. Department of Clinical Research Medicine, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan. toshihiro.nanki@med.toho-u.ac.jp.
Abstract
OBJECTIVES: Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to cell surface receptors (S1P1-5). In this study, we examined the effect of S1P1 agonist, 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 S1P1 was 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.
OBJECTIVES:Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to cell surface receptors (S1P1-5). In this study, we examined the effect of S1P1 agonist, ONO-W061, on murineCandida albicanswater-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 S1P1 was 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: T Komiya; K Sato; H Shioya; Y Inagaki; H Hagiya; R Kozaki; M Imai; Y Takada; T Maeda; H Kurata; M Kurono; R Suzuki; K Otsuki; H Habashita; S Nakade Journal: Clin Exp Immunol Date: 2013-01 Impact factor: 4.330