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A sphingosine 1-phosphate receptor agonist ameliorates animal model of vasculitis

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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.

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Authors and Affiliations

  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

    Chie Miyabe, Yoshishige Miyabe, Nobuyuki Miyasaka & Toshihiro Nanki

  2. Department of Dermatology, Tokyo Medical University, 6-7-1, Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Chie Miyabe & Ryoji Tsuboi

  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

    Chie Miyabe, Yoshishige Miyabe & Andrew D. Luster

  4. Department of Biology and Pharmacology, Ono Pharmaceutical Co. Ltd, 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan

    Takaki Komiya & Hiroki Shioya

  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

    Noriko N. Miura & Naohito Ohno

  6. Department of Pathology, Toho University, 2-17-6 Ohashi, Meguro, Tokyo, 153-8515, Japan

    Kei Takahashi

  7. Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan

    Shinichi Kawai & Toshihiro Nanki

  8. Department of Clinical Research Medicine, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo, 173-8605, Japan

    Toshihiro Nanki

Authors
  1. Chie Miyabe
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  2. Yoshishige Miyabe
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  3. Takaki Komiya
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  4. Hiroki Shioya
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  5. Noriko N. Miura
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  6. Kei Takahashi
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  7. Naohito Ohno
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  8. Ryoji Tsuboi
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  9. Andrew D. Luster
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  10. Shinichi Kawai
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  11. Nobuyuki Miyasaka
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  12. Toshihiro Nanki
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Corresponding author

Correspondence to Toshihiro Nanki.

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Conflict of interest

Chie Miyabe, Yoshishige Miyabe, Takaki Komiya, Hiroki Shioya, Noriko N. Miura, Kei Takahashi, Naohito Ohno, Ryoji Tsuboi and Andrew. D Luster have nothing to disclose. Shinichi Kawai has received research Grants from AbbVie Inc., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co Ltd., Teijin Pharma Ltd., Eli Lilly Japan K.K. and speaking fees from AbbVie Inc., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Zoki Pharmaceutical Co., Ltd., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., and Pfizer Japan Inc., outside the submitted work. Nobuyuki Miyasaka reports Grants from Mitsubishi Tanabe pharmaceuticals, Grants from Chugai Pharmaceuticals, Grants from Takeda Pharmaceuticals, outside the submitted work. Toshihiro Nanki has received consulting fee, speaking fee, and/or honoraria from Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co. Ltd., Astellas Pharma Inc., AbbVie Inc., Janssen Pharma K.K., Bristol-Myers Squibb, Daiichi Sankyo Co. Ltd., Santen Pharmaceutical Co., Ltd. and UCB Japan Co., Ltd., and has received research Grant support from Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Teijin Pharma Ltd., Eli Lilly Japan K.K., Bristol-Myers Squibb and AbbVie Inc.

Funding

This work was supported in part by the Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases at Tokyo Medical and Dental University.

Additional information

Responsible Editor: Yoshiya Tanaka.

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Miyabe, C., Miyabe, Y., Komiya, T. et al. A sphingosine 1-phosphate receptor agonist ameliorates animal model of vasculitis. Inflamm. Res. 66, 335–340 (2017). https://doi.org/10.1007/s00011-016-1018-y

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  • DOI: https://doi.org/10.1007/s00011-016-1018-y

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