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

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. 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. 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. 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.

Citation

Chie Miyabe, Yoshishige Miyabe, Takaki Komiya, Hiroki Shioya, Noriko N Miura, Kei Takahashi, Naohito Ohno, Ryoji Tsuboi, Andrew D Luster, Shinichi Kawai, Nobuyuki Miyasaka, Toshihiro Nanki. A sphingosine 1-phosphate receptor agonist ameliorates animal model of vasculitis. Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2017 Apr;66(4):335-340

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PMID: 27942751

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