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Rapamycin Ameliorates Experimental Autoimmune Encephalomyelitis by Suppressing the mTOR-STAT3 Pathway.
Neurochem Res 2017; 42(10):2831-2840NR

Abstract

Rapamycin is a new immunosuppressant that has a primarily anti-inflammatory effect and selectively inhibits the activation of T helper (Th)-cell subsets. It is widely used to treat autoimmune disease. We studied the mechanism of rapamycin action against experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a classic animal model of multiple sclerosis. Rapamycin significantly inhibited the development of EAE by decreasing both clinical scores and inflammatory cell infiltration into the spinal cord. Furthermore, rapamycin reversed EAE symptoms in mice showing the initial signs of paralysis. Rapamycin, is a mammalian target of rapamycin (mTOR) inhibitor. By measuring the downstream markers phospho-mTOR (p-mTOR)/mTOR and phospho-signal transducer and activator of transcription 3 (p-STAT3)/STAT3, we showed that rapamycin suppressed the mTOR-STAT3 pathway in EAE mice. The mTOR-STAT3 signaling pathway is important for Th1 and Th17 cell responses. We found that rapamycin-treated mice had reduced proportions of Th1 and Th17 cells, as well as lower mRNA expression for the transcription factors T-bet and RoRγt in EAE mouse splenocytes. To evaluate Th1 and Th17 cell function, we examined expression of their specific cytokines in the peripheral immune system and central nervous system. Rapamycin treatment reduced protein and mRNA levels of interferon (IFN)-γand interleukin (IL)-17 in splenocytes, and reduced IFN-γ and IL-17 mRNA levels in the spinal cords of EAE mice. These findings suggest that rapamycin treatment inhibits the mTOR-STAT3 pathway in EAE mice, thereby promoting immunosuppression. This study may provide new insight into the mechanism controlling rapamycin effects in multiple sclerosis.

Authors+Show Affiliations

Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.Department of Neurosurgery, North China Petroleum Bureau General Hospital of Hebei Medical University, Renqiu, 062552, Hebei, China.Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.Emergency Department, 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.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. guoli6105@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28600752

Citation

Hou, Huiqing, et al. "Rapamycin Ameliorates Experimental Autoimmune Encephalomyelitis By Suppressing the mTOR-STAT3 Pathway." Neurochemical Research, vol. 42, no. 10, 2017, pp. 2831-2840.
Hou H, Miao J, Cao R, et al. Rapamycin Ameliorates Experimental Autoimmune Encephalomyelitis by Suppressing the mTOR-STAT3 Pathway. Neurochem Res. 2017;42(10):2831-2840.
Hou, H., Miao, J., Cao, R., Han, M., Sun, Y., Liu, X., & Guo, L. (2017). Rapamycin Ameliorates Experimental Autoimmune Encephalomyelitis by Suppressing the mTOR-STAT3 Pathway. Neurochemical Research, 42(10), pp. 2831-2840. doi:10.1007/s11064-017-2296-7.
Hou H, et al. Rapamycin Ameliorates Experimental Autoimmune Encephalomyelitis By Suppressing the mTOR-STAT3 Pathway. Neurochem Res. 2017;42(10):2831-2840. PubMed PMID: 28600752.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapamycin Ameliorates Experimental Autoimmune Encephalomyelitis by Suppressing the mTOR-STAT3 Pathway. AU - Hou,Huiqing, AU - Miao,Jun, AU - Cao,Runjing, AU - Han,Mei, AU - Sun,Yafei, AU - Liu,Xiaoqian, AU - Guo,Li, Y1 - 2017/05/30/ PY - 2016/04/06/received PY - 2016/09/15/accepted PY - 2017/6/11/pubmed PY - 2018/8/8/medline PY - 2017/6/11/entrez KW - Experimental autoimmune encephalomyelitis KW - Multiple sclerosis KW - Rapamycin KW - Th1 cell KW - Th17 cell KW - mTOR SP - 2831 EP - 2840 JF - Neurochemical research JO - Neurochem. Res. VL - 42 IS - 10 N2 - Rapamycin is a new immunosuppressant that has a primarily anti-inflammatory effect and selectively inhibits the activation of T helper (Th)-cell subsets. It is widely used to treat autoimmune disease. We studied the mechanism of rapamycin action against experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a classic animal model of multiple sclerosis. Rapamycin significantly inhibited the development of EAE by decreasing both clinical scores and inflammatory cell infiltration into the spinal cord. Furthermore, rapamycin reversed EAE symptoms in mice showing the initial signs of paralysis. Rapamycin, is a mammalian target of rapamycin (mTOR) inhibitor. By measuring the downstream markers phospho-mTOR (p-mTOR)/mTOR and phospho-signal transducer and activator of transcription 3 (p-STAT3)/STAT3, we showed that rapamycin suppressed the mTOR-STAT3 pathway in EAE mice. The mTOR-STAT3 signaling pathway is important for Th1 and Th17 cell responses. We found that rapamycin-treated mice had reduced proportions of Th1 and Th17 cells, as well as lower mRNA expression for the transcription factors T-bet and RoRγt in EAE mouse splenocytes. To evaluate Th1 and Th17 cell function, we examined expression of their specific cytokines in the peripheral immune system and central nervous system. Rapamycin treatment reduced protein and mRNA levels of interferon (IFN)-γand interleukin (IL)-17 in splenocytes, and reduced IFN-γ and IL-17 mRNA levels in the spinal cords of EAE mice. These findings suggest that rapamycin treatment inhibits the mTOR-STAT3 pathway in EAE mice, thereby promoting immunosuppression. This study may provide new insight into the mechanism controlling rapamycin effects in multiple sclerosis. SN - 1573-6903 UR - https://www.unboundmedicine.com/medline/citation/28600752/Rapamycin_Ameliorates_Experimental_Autoimmune_Encephalomyelitis_by_Suppressing_the_mTOR_STAT3_Pathway_ L2 - https://doi.org/10.1007/s11064-017-2296-7 DB - PRIME DP - Unbound Medicine ER -