PMID- 28600752
OWN - NLM
STAT- MEDLINE
DCOM- 20180807
LR  - 20211204
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 42
IP  - 10
DP  - 2017 Oct
TI  - Rapamycin Ameliorates Experimental Autoimmune Encephalomyelitis by Suppressing 
      the mTOR-STAT3 Pathway.
PG  - 2831-2840
LID - 10.1007/s11064-017-2296-7 [doi]
AB  - 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 RoRgammat 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)-gammaand interleukin (IL)-17 in splenocytes, and reduced 
      IFN-gamma 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.
FAU - Hou, Huiqing
AU  - Hou H
AD  - Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital 
      of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
FAU - Miao, Jun
AU  - Miao J
AD  - Department of Neurosurgery, North China Petroleum Bureau General Hospital of 
      Hebei Medical University, Renqiu, 062552, Hebei, China.
FAU - Cao, Runjing
AU  - Cao R
AD  - Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital 
      of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
FAU - Han, Mei
AU  - Han M
AD  - Emergency Department, The Second Hospital of Hebei Medical University, 
      Shijiazhuang, 050000, Hebei, China.
FAU - Sun, Yafei
AU  - Sun Y
AD  - Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital 
      of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
FAU - Liu, Xiaoqian
AU  - Liu X
AD  - Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital 
      of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
FAU - Guo, Li
AU  - Guo L
AD  - Department of Neurology, Key Laboratory of Hebei Neurology, The Second Hospital 
      of Hebei Medical University, Shijiazhuang, 050000, Hebei, China. 
      guoli6105@163.com.
LA  - eng
GR  - 81100884/National Natural Science Foundation of China/
GR  - 20150213/key project of Medical Science Research in Hebei Province/
PT  - Journal Article
DEP - 20170530
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Cytokines)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (STAT3 Transcription Factor)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Central Nervous System/*drug effects/metabolism
MH  - Cytokines/metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/*drug therapy
MH  - Female
MH  - Interferon-gamma/pharmacology
MH  - Mice, Inbred C57BL
MH  - Multiple Sclerosis/drug therapy
MH  - Myelin-Oligodendrocyte Glycoprotein/metabolism
MH  - STAT3 Transcription Factor/drug effects/*metabolism
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/drug effects/metabolism
OTO - NOTNLM
OT  - Experimental autoimmune encephalomyelitis
OT  - Multiple sclerosis
OT  - Rapamycin
OT  - Th1 cell
OT  - Th17 cell
OT  - mTOR
EDAT- 2017/06/11 06:00
MHDA- 2018/08/08 06:00
CRDT- 2017/06/11 06:00
PHST- 2016/04/06 00:00 [received]
PHST- 2016/09/15 00:00 [accepted]
PHST- 2017/06/11 06:00 [pubmed]
PHST- 2018/08/08 06:00 [medline]
PHST- 2017/06/11 06:00 [entrez]
AID - 10.1007/s11064-017-2296-7 [pii]
AID - 10.1007/s11064-017-2296-7 [doi]
PST - ppublish
SO  - Neurochem Res. 2017 Oct;42(10):2831-2840. doi: 10.1007/s11064-017-2296-7. Epub 
      2017 May 30.