Kirenol Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Differentiation of Th1 and Th17 Cells and Inducing Apoptosis of Effector T Cells

被引:26
作者
Xiao, Juan [1 ,2 ,3 ]
Yang, Rongbing [2 ]
Yang, Lin [1 ]
Fan, Xiaohang [1 ]
Liu, Wenwei [1 ]
Deng, Wenbin [1 ,3 ]
机构
[1] Hubei Univ Arts & Sci, Coll Med, Xiangyang, Hubei, Peoples R China
[2] Handan Cent Hosp, Dept Biol Treatment, Handan, Hebei, Peoples R China
[3] Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Davis, CA 95616 USA
来源
SCIENTIFIC REPORTS | 2015年 / 5卷
基金
美国国家卫生研究院;
关键词
COLLAGEN-INDUCED ARTHRITIS; INFLAMMATION; DEATH; PATHOGENESIS;
D O I
10.1038/srep09022
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is characterized by CNS demyelination mediated by autoreactive T cells. Kirenol, a biologically active substance isolated from Herba Siegesbeckiae, has potent anti-inflammatory activities. Here we investigated effects of kirenol on EAE. Kirenol treatment markedly delayed onset of disease and reduced clinical scores in EAE mice. Kirenol treatment reduced expression of IFN-gamma and IL-17A in the serum and proportion of Th1 and Th17 cells in draining lymph nodes. Priming of lymphocytes was reduced and apoptosis of MOG-activated CD41T cells was increased in kirenol treated EAE mice. Kirenol treatment of healthy animals did not affect the lymphocytes in these non-immunized mice. Further in vitro studies showed that kirenol inhibited viability of MOG-specific lymphocytes and induced apoptosis of MOG-specific CD41 T cells in a dose-and time-dependent manner. Kirenol treatment upregulated Bax, downregulated Bcl-2, and increased activation of caspase-3 and release of cytochrome c, indicating that a mitochondrial pathway was involved in kirenol induced apoptosis. Moreover, pretreatment with either a pan-caspase inhibitor z-VAD-fmk or a more specific caspase 3 inhibitor Ac-DEVD-CHO in lymphocytes reduced kirenol induced apoptosis. Our findings implicate kirenol as a useful agent for the treatment of MS.
引用
收藏
页数:8
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