Effects of the novel immunosuppressant FTY720 in a murine rheumatoid arthritis model |
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| Authors: | Sachi Tsunemi Tsuyoshi Iwasaki Sachie Kitano Takehito Imado Keiji Miyazawa Hajime Sano |
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| Affiliation: | 1. Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan;2. Division of Pharmacotherapy, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, 650-8530, Japan;3. Discovery Research III, Research and Development, Kissei Pharmaceutical Co Ltd, 4365-1 Hotakakashiwabara, Azumino, Nagano, 399-8304, Japan |
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| Abstract: | We investigated the effects and mechanisms by which FTY720 (FTY) inhibits arthritis development in the SKG mouse rheumatoid arthritis (RA) model. FTY (1 mg/kg/day) administration suppressed the progression of laminarin-induced arthritis in SKG mice. FTY treatment decreased IL-6 and TNF-α expression in synovial fibroblast cells and the number of inflammatory cells overall. Bone destruction was also suppressed by treatment with FTY. The numbers of CD4+ and CD8+ T cells were significantly increased in the thymus and decreased in the spleen in FTY-treated SKG mice. FTY enhanced IL-4 production by CD4+ T cells stimulated by allogeneic spleen cells and inhibited prostaglandin E2 (PGE2) production by a TNF-α-stimulated synovial fibroblast cell line. These results indicate that FTY can inhibit arthritis in SKG mice via sequestration of autoimmune CD4+ T cells in the thymus, enhancement of Th2 immune responses, and inhibition of PGE2 production by synovial cells. |
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| Keywords: | DC, dendritic cell S1P, sphingosine 1-phosphate Tregs, regulatory T cells MLR, mixed lymphocyte reaction RA, rheumatoid arthritis |
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