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Tripchlorolide ameliorates experimental autoimmune encephalomyelitis by down-regulating ERK1/2-NF-κB and JAK/STAT signaling pathways
被引:31
|作者:
Zhang, Jian
[1
,2
]
Zeng, Yu-qi
[1
,2
]
Zhang, Jing
[1
,2
]
Pan, Xiao-dong
[1
,2
]
Kang, De-yong
[3
]
Huang, Tian-wen
[1
,2
]
Chen, Xiao-chun
[1
,2
]
机构:
[1] Fujian Med Univ, Union Hosp, Fujian Inst Geriatr, Dept Neurol & Geriatr, Fuzhou 350001, Fujian, Peoples R China
[2] Fujian Med Univ, Union Hosp, Fujian Key Lab Mol Neurol, Key Lab Brain Aging & Neurodegenerat Dis, Fuzhou 350001, Fujian, Peoples R China
[3] Fujian Med Univ, Union Hosp, Dept Pathol, Fuzhou 350001, Fujian, Peoples R China
基金:
中国国家自然科学基金;
关键词:
cytokine;
experimental autoimmune encepha-lomyelitis;
JAK;
STAT pathway;
NF-B pathway;
transcription factor;
tripchlorolide;
NF-KAPPA-B;
MULTIPLE-SCLEROSIS LESIONS;
EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS;
T-CELLS;
MICROARRAY ANALYSIS;
ANIMAL-MODELS;
MICE;
DISEASE;
ACTIVATION;
NEUROTOXICITY;
D O I:
10.1111/jnc.13058
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Tripchlorolide (T4), an extract of the natural herb Tripterygium wilfordii Hook F, has been found to possess anti-inflammatory and immunosuppressive actions. In the current study, these actions were evaluated in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis by scoring the clinical signs, observing the infiltration of inflammatory cells and myelin sheath in the lumbar spinal cord of EAE mice. The results demonstrated that T4 (at a dose of 40g/kg) significantly reduced the severity of EAE and slowed down the ongoing EAE. Further analysis showed that T4 suppressed the mRNA and protein levels of the transcription factors T-bet and RoRrt and mRNA levels of IFN- and IL-17 in the spinal cords. Furthermore, T4 down-regulated the ERK1/2-NF-B and JAK/STAT signaling pathways. At 40g/kg, T4 did not induce side effects on hematological parameters. These findings suggest that T4 ameliorates EAE by immunosuppression, providing a new insight into T4 application in multiple sclerosis treatment.
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页码:104 / 112
页数:9
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