雷帕霉素和芬戈莫德通过调节 Akt-mTOR 和 MAPK/ERK 通路调节实验性自身免疫性脑脊髓炎中的 Treg/Th17 细胞。
Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways.
机构信息
Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
出版信息
J Neuroimmunol. 2018 Nov 15;324:26-34. doi: 10.1016/j.jneuroim.2018.08.012. Epub 2018 Aug 27.
Rapamycin prevents experimental autoimmune encephalomyelitis (EAE) and activates the MAPK/ERK pathway in EAE. Thus, we hypothesized combining rapamycin and fingolimod treatments would have synergistic effects in EAE. We show that combination therapy ameliorated EAE and regulated spinal cord IL-17 and TGF-β levels in EAE mice. Combination therapy also modulated IL-17 and TGF-β concentration, RoRγt and Foxp3 mRNA levels, and Th17 cell and Treg frequencies in the spleen. Moreover, rapamycin decreased ps6k and increased pAkt and pERK, while combination therapy downregulated pAkt, ps6 k and pERK in EAE mice. Our findings provide insight into using this drug combination to treat EAE.
雷帕霉素可预防实验性自身免疫性脑脊髓炎（EAE）并激活 EAE 中的 MAPK/ERK 通路。因此，我们假设雷帕霉素和芬戈莫德联合治疗在 EAE 中具有协同作用。我们发现联合治疗可改善 EAE 并调节 EAE 小鼠脊髓中的白细胞介素 17（IL-17）和转化生长因子-β（TGF-β）水平。联合治疗还调节了白细胞介素 17和转化生长因子-β浓度、RoRγt 和 Foxp3 mRNA 水平以及脾中 Th17 细胞和 Treg 频率。此外，雷帕霉素降低了 ps6k 并增加了 pAkt 和 pERK，而联合治疗则下调了 EAE 小鼠中的 pAkt、ps6k 和 pERK。我们的研究结果为使用这种药物联合治疗 EAE 提供了思路。
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