Effects of the novel immunosuppressant FTY720 in a murine rheumatoid arthritis model
Effects of the novel immunosuppressant FTY720 in a murine rheumatoid arthritis model
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DOI：
10.1016/j.clim.2010.03.428
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发表时间：
2010-08-01
影响因子：
8.6
通讯作者：
Sano, Hajime
中科院分区：
文献类型：
--
作者：
Tsunemi, Sachi;Iwasaki, Tsuyoshi;Sano, Hajime
我们研究了FTY 720（FTY）抑制SKG小鼠类风湿性关节炎（RA）模型中关节炎发展的作用和机制。FTY（1 mg/kg/天）给药可抑制SKG小鼠中昆布多糖诱导的关节炎的进展。FTY治疗降低了滑膜成纤维细胞中IL-6和TNF-α的表达以及总体炎性细胞的数量。FTY治疗也抑制了骨破坏。FTY处理后，SKG小鼠胸腺中CD 4（+）和CD 8（+）T细胞数量显著增加，脾脏中CD 4（+）和CD 8（+）T细胞数量显著减少。FTY增强同种异体脾细胞刺激的CD 4（+）T细胞产生IL-4，并抑制TNF-α刺激的滑膜成纤维细胞系产生前列腺素E-2（PGE（2））。这些结果表明FTY可以通过隔离胸腺中的自身免疫CD 4（+）T细胞、增强Th 2免疫应答和抑制滑膜细胞产生PGE（2）来抑制SKG小鼠的关节炎。(C)2010年爱思唯尔公司All rights reserved.
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-alpha 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 E-2 (PGE(2)) production by a TNF-alpha-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 PGE(2) production by synovial cells. (C) 2010 Elsevier Inc. All rights reserved.