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

Juan Xiao,Rongbing Yang,Lin Yang,Xiaohang Fan,Wenwei Liu,W. Deng

Published 2015 in Scientific Reports

ABSTRACT

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-γ 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 CD4+ T cells was increased in kirenol treated EAE mice. Kirenol treatment of healthy animals did not affect the lymphocytes in these non-immunized mice. Further invitro studies showed that kirenol inhibited viability of MOG-specific lymphocytes and induced apoptosis of MOG-specific CD4+ 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.

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