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

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.

• Authors: 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
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 66 Issue 4 Pg. 335-340 (Apr 2017) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 27942751 (Publication Type: Journal Article)

Chemical References

• CXCL8 protein, human
• Chemokine CXCL1
• Interleukin-8
• Lysophospholipids
• Receptors, Lysosphingolipid
• sphingosine 1-phosphate
• Sphingosine

Topics

• Animals
• Candida albicans
• Chemokine CXCL1 (metabolism)
• Disease Models, Animal
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Interleukin-8 (metabolism)
• Leukocyte Count
• Lysophospholipids (metabolism)
• Male
• Mice, Inbred BALB C
• Receptors, Lysosphingolipid (agonists)
• Sphingosine (analogs & derivatives, metabolism)
• Vasculitis (drug therapy, immunology, metabolism)