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Fingolimod phosphate promotes the neuroprotective effects of microglia

机译:磷酸芬戈莫德促进小胶质细胞的神经保护作用

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Fingolimod phosphate (FTY720) is a sphingosine 1-phosphate (S1P) receptor agonist that is being used as a new oral drug for multiple sclerosis. FTY720 prevents lymphocytes from moving out of the lymphoid organs and inhibits autoreactive lymphocytes from infiltrating the central nervous system. Whether FTY720 directly affects microglia-the innate immune cells of the central nervous system-is unclear. Here we show that FTY720 binds S1P1 receptors to downregulate activated microglial production of such pro-inflammatory cytokines as tumor necrosis factor-??, interleukin-1??, and interleukin-6. FTY720 also upregulates microglial production of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor. These results suggested that FTY720 directly promotes the neuroprotective effects of microglia. Therefore, FTY720 may be a potent therapeutic agent for not only multiple sclerosis but also other neurologic diseases associated with microglial activation. ? 2012 Elsevier B.V..
机译:磷酸芬戈莫德(FTY720)是一种鞘氨醇1-磷酸(S1P)受体激动剂,被用作治疗多发性硬化症的新型口服药物。 FTY720可防止淋巴细胞移出淋巴器官,并抑制自身反应性淋巴细胞浸润中枢神经系统。 FTY720是否直接影响小胶质细胞-中枢神经系统的先天免疫细胞-尚不清楚。在这里,我们显示FTY720结合S1P1受体以下调诸如肿瘤坏死因子-β,白介素-1β和白介素-6之类的促炎细胞因子的活化小胶质细胞产生。 FTY720还上调了脑源性神经营养因子和胶质细胞源性神经营养因子的小胶质细胞生成。这些结果表明FTY720直接促进小胶质细胞的神经保护作用。因此,FTY720不仅是多发性硬化症的有效治疗剂,而且还是与小胶质细胞活化相关的其他神经系统疾病的有效治疗剂。 ? 2012年Elsevier B.V ..

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