Rapamycin Alleviates the Symptoms of Multiple Sclerosis in Experimental Autoimmune Encephalomyelitis (EAE) Through Mediating the TAM-TLRs-SOCS Pathway.
Rapamycin Alleviates the Symptoms of Multiple Sclerosis in Experimental Autoimmune Encephalomyelitis (EAE) Through Mediating the TAM-TLRs-SOCS Pathway.
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DOI：
10.3389/fneur.2020.590884
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发表时间：
2020
影响因子：
3.4
通讯作者：
Wang MX
中科院分区：
文献类型：
--
作者：
Li XL;Zhang B;Liu W;Sun MJ;Zhang YL;Liu H;Wang MX
多发性硬化（MS）是中枢神经系统（CNS）的炎性脱髓鞘疾病。本研究采用人工合成的髓鞘少突胶质细胞糖蛋白肽35-55（MOG 35 -55）诱导实验性自身免疫性脑脊髓炎（EAE）小鼠模型，观察其对MS的免疫调节作用。将50只C57 BL/6小鼠随机分为正常组、EAE组和雷帕霉素组（EAE小鼠用3种不同剂量的雷帕霉素处理）。在免疫后21天对小鼠的脑组织进行苏木精和伊红染色以及Weil髓鞘染色。采用免疫组化方法检测室旁组织中Gas 6、Tyro 3、Axl、Mer蛋白的表达。采用实时定量PCR（qRT-PCR）和Western blot分别检测Gas 6、Tyro 3、Axl、Mer、SOCS 1、SOCS 3、Toll样受体（TLR）3和TLR 4的mRNA和蛋白表达。采用酶联免疫吸附试验（ELISA）检测炎症因子IFN-γ和IL-17的分泌。雷帕霉素治疗可改善MOG 35 -55诱导的EAE小鼠的行为学障碍。免疫后21 d，EAE小鼠Gas 6、Tyro 3、Axl、Mer、SOCS 1和SOCS 3的表达均降低，而雷帕霉素组Gas 6、Tyro 3、Axl和Mer的表达均高于EAE组。伴随着抗炎蛋白SOCS 1和SOCS 3的增加，炎性蛋白TLR-3、TLR-4以及IFN-γ和IL-17的量的减少。雷帕霉素注射可减轻EAE小鼠神经功能和髓鞘丢失，主要通过介导TAM-TLRs-SOCS信号通路调节天然免疫。
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Our research aimed to find an immunomodulatory therapy for MS. An experimental autoimmune encephalomyelitis (EAE) mouse model of MS was established induced with the syntheticmyelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Fifty C57BL/6 mice were randomly divided into the Normal group, EAE group, and Rapamycin group (EAE mice treated with three different doses of rapamycin). Hematoxylin and eosin staining and Weil myelin staining were performed on the brain tissues of mice after 21 days post-immunization. The protein expression of Gas6, Tyro3, Axl, Mer in paraventricular tissues were analyzed by immunohistochemistry. The mRNA and protein expression of Gas6, Tyro3, Axl, Mer, SOCS1, SOCS3, Toll-like receptor (TLR) 3, and TLR4 were detected by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. An enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of the inflammatory factors IFN-γ and IL-17. Rapamycin treatment could ameliorate the behavior impairment in EAE mice induced by MOG35-55. The expression of Gas6, Tyro3, Axl, Mer, SOCS1, and SOCS3 were decreased in EAE mice at 21 days post-immunization, while the expression of Gas6, Tyro3, Axl, and Mer in rapamycin group was higher than that in EAE group. It was accompanied by an increase in anti-inflammatory proteins SOCS1 and SOCS3, a decrease in the inflammatory proteins TLR-3, TLR-4 and in the amount of IFN-γ, and IL-17. Rapamycin injection relieved the nerve function of and the loss of myelin sheath in the EAE mice, mainly through mediating the TAM-TLRs-SOCS signaling pathway to regulate natural immunity.
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影响因子：
5.3
作者：
MANFIOLETTI, G;BRANCOLINI, C;SCHNEIDER, C
通讯作者：
SCHNEIDER, C
影响因子：
2.7
作者：
Lana, D.;Di Russo, J.;Mello, T.;Wenk, G. L.;Giovannini, M. G.
通讯作者：
Giovannini, M. G.
影响因子：
3.4
作者：
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通讯作者：
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影响因子：
32.4
作者：
Carrera Silva EA;Chan PY;Joannas L;Errasti AE;Gagliani N;Bosurgi L;Jabbour M;Perry A;Smith-Chakmakova F;Mucida D;Cheroutre H;Burstyn-Cohen T;Leighton JA;Lemke G;Ghosh S;Rothlin CV
通讯作者：
Rothlin CV
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
影响因子：
3.3
作者：
Hou, Huiqing;Cao, Runjing;Song, Xiujuan
通讯作者：
Song, Xiujuan