Since microglia-associated neuroinflammation plays a pivotal role in the progression of white matter diseases, modulating microglial activation has been suggested as a potential therapeutic strategy. Here, we investigated the anti-inflammatory effects of fingolimod (FTY720) on microglia and analyzed the crosstalk between microglia autophagy and neuroinflammation. Lipopolysaccharide (LPS)-induced primary cultured microglia model was established. Microglial phenotypes were assessed by Western blot, quantitative real-time polymerase chain reaction (RT-PCR) and flow cytometry. Autophagy was evaluated by immunofluorescence, MDC staining and Western blot. Rapamycin was used to investigate the role of autophagic process in regulating microglial phenotypes. The signaling markers were screened by RT-PCR and Western blot. FTY720 shifted microglial phenotype from pro-inflammatory state to anti-inflammatory state and inhibited microglial autophagy under lipopolysaccharide (LPS) treatment. Rapamycin reversed the effect of FTY720 on phenotype transformation of microglia. The results of mechanism studies have shown that FTY720 notably repressed LPS-induced STAT1 activity, which was reactivated by rapamycin. Our research suggested that FTY720 could significantly transform pro-inflammatory microglia into anti-inflammatory microglia by suppressing autophagy via STAT1.

中文翻译：

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FTY720 通过 STAT1 通路抑制自噬来调节小胶质细胞的抗炎表型。

由于小胶质细胞相关的神经炎症在白质疾病的进展中起着关键作用，因此调节小胶质细胞激活被认为是一种潜在的治疗策略。在这里，我们研究了芬戈莫德 (FTY720) 对小胶质细胞的抗炎作用，并分析了小胶质细胞自噬与神经炎症之间的串扰。建立脂多糖（LPS）诱导的原代培养小胶质细胞模型。通过蛋白质印迹、定量实时聚合酶链反应 (RT-PCR) 和流式细胞术评估小胶质细胞表型。通过免疫荧光、MDC 染色和蛋白质印迹评估自噬。雷帕霉素用于研究自噬过程在调节小胶质细胞表型中的作用。通过RT-PCR和Western印迹筛选信号标记。FTY720 将小胶质细胞表型从促炎状态转变为抗炎状态，并在脂多糖 (LPS) 处理下抑制小胶质细胞自噬。雷帕霉素逆转了 FTY720 对小胶质细胞表型转化的影响。机制研究结果表明，FTY720 显着抑制 LPS 诱导的 STAT1 活性，该活性被雷帕霉素重新激活。我们的研究表明，FTY720 可以通过 STAT1 抑制自噬，显着将促炎小胶质细胞转化为抗炎小胶质细胞。机制研究结果表明，FTY720 显着抑制 LPS 诱导的 STAT1 活性，该活性被雷帕霉素重新激活。我们的研究表明，FTY720 可以通过 STAT1 抑制自噬，显着将促炎小胶质细胞转化为抗炎小胶质细胞。机制研究结果表明，FTY720 显着抑制 LPS 诱导的 STAT1 活性，该活性被雷帕霉素重新激活。我们的研究表明，FTY720 可以通过 STAT1 抑制自噬，显着将促炎小胶质细胞转化为抗炎小胶质细胞。