The Antiepileptic Drug Valproic Acid Restores T Cell Homeostasis and Ameliorates Pathogenesis of Experimental Autoimmune Encephalomyelitis

doi:10.1074/jbc.M112.356584

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	The Antiepileptic Drug Valproic Acid Restores T Cell Homeostasis and Ameliorates Pathogenesis of Experimental Autoimmune Encephalomyelitis
	Lv, Jie 3; Du, Changsheng 3; Wei, Wei 1,3; Wu, Zhiying 2,4; Zhao, Guixian 2,4; Li, Zhenxin 2,4; Xie, Xin1,3
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2012-08-17
卷号	287 期号:34 页码:28656-28665
ISSN号	0021-9258
DOI	10.1074/jbc.M112.356584
文献子类	Article
英文摘要	Maintaining a constant number and ratio of immune cells is one critical aspect of the tight regulation of immune homeostasis. Breakdown of this balance will lead to autoimmune diseases such as multiple sclerosis (MS). The antiepileptic drug valproic acid (VPA) was reported to regulate the growth, survival, and differentiation of many cells. However, its function in T cell homeostasis and MS treatment remains unknown. In this study, VPA was found to reduce spinal cord inflammation, demyelination, and disease scores in experimental autoimmune encephalomyelitis, a mouse model of MS. Further study indicated that VPA induces apoptosis in activated T cells and maintains the immune homeostasis. This effect was found to be mainly mediated by the caspase-8/caspase-3 pathway. Interestingly, this phenomenon was also confirmed in T cells from normal human subjects and MS patients. Considering the long history of clinical use and our new findings, we believe VPA might be a safe and effective therapy for autoimmune diseases, such as multiple sclerosis.
资助项目	National Natural Science Foundation of China[31000399] ; National Natural Science Foundation of China[31171348] ; National Natural Science Foundation of China[31071227] ; National Natural Science Foundation of China[81100963] ; 973 Program[2012CB910404] ; Ministry of Science and Technology of China[2009ZX09302-001]
WOS关键词	HISTONE DEACETYLASE INHIBITORS ; MULTIPLE-SCLEROSIS ; IMMUNE HOMEOSTASIS ; TRICHOSTATIN-A ; TGF-BETA ; APOPTOSIS ; THERAPY ; SYSTEM ; BCL-2 ; HDAC
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000308074600039
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277985]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Xie, Xin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Fudan Univ, Shanghai Med Coll, Huashan Hosp, Inst Neurol, Shanghai 200040, Peoples R China 3.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Lab Receptor Based Biomed, Sch Life Sci & Technol, Shanghai 200092, Peoples R China; 4.Fudan Univ, Shanghai Med Coll, Huashan Hosp, Dept Neurol, Shanghai 200040, Peoples R China;
推荐引用方式 GB/T 7714	Lv, Jie,Du, Changsheng,Wei, Wei,et al. The Antiepileptic Drug Valproic Acid Restores T Cell Homeostasis and Ameliorates Pathogenesis of Experimental Autoimmune Encephalomyelitis[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(34):28656-28665.
APA	Lv, Jie.,Du, Changsheng.,Wei, Wei.,Wu, Zhiying.,Zhao, Guixian.,...&Xie, Xin.(2012).The Antiepileptic Drug Valproic Acid Restores T Cell Homeostasis and Ameliorates Pathogenesis of Experimental Autoimmune Encephalomyelitis.JOURNAL OF BIOLOGICAL CHEMISTRY,287(34),28656-28665.
MLA	Lv, Jie,et al."The Antiepileptic Drug Valproic Acid Restores T Cell Homeostasis and Ameliorates Pathogenesis of Experimental Autoimmune Encephalomyelitis".JOURNAL OF BIOLOGICAL CHEMISTRY 287.34(2012):28656-28665.