Artemisinin Analogue SM934 Ameliorates Murine Experimental Autoimmune Encephalomyelitis through Enhancing the Expansion and Functions of Regulatory T Cell

doi:10.1371/journal.pone.0074108

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Artemisinin Analogue SM934 Ameliorates Murine Experimental Autoimmune Encephalomyelitis through Enhancing the Expansion and Functions of Regulatory T Cell
	Li, Xin 1; Li, Tian-Tian 1; Zhang, Xiao-Hui 2; Hou, Li-Fei 1; Yang, Xiao-Qian 1; Zhu, Feng-Hua 1; Tang, Wei1 ; Zuo, Jian-Ping2
刊名	PLOS ONE
	2013-08-29
卷号	8 期号:8
ISSN号	1932-6203
DOI	10.1371/journal.pone.0074108
文献子类	Article
英文摘要	Background: Artemisinin analogue SM934 was previously reported to possess immunosuppressive properties. The aim of this study was to determine the effects and the underlying mechanisms of SM934 in murine experimental autoimmune encephalomyelitis (EAE). Methods: Female C57BL/6 mice immunized with MOG(35-55) were treated with or without SM934, then the clinical scores and other relevant parameters were assessed. Th1, Th17 and regulatory T (Treg) cell profiles were determined through ELISA, qRT-PCR, flow cytometry and BrdU incorporation assay. The effects of SM934 on Th1, Th17 and Treg cells differentiation were explored through intracellular staining and flow cytometry examination. Results: In vivo, administration of SM934 significantly inhibited the development of EAE and suppressed the elevation of serum IL-17. Ex vivo, upon antigen-recall stimulation, IL-2, IFN-gamma, IL-17 and IL-6 production were decreased, whereas IL-10 and TGF-beta production were increased from the splenocytes isolated from SM934-treated mice. Consistently, both flow cytometry and qRT-PCR results showed that SM934 treatment significantly increased the Treg, while strongly suppressed the Th17 and Th1, responses in the peripheral. Furthermore, in the spinal lesion, SM934 treatment dramatically decreased the infiltration of CD4(+) T cells, within which the Treg cells percentage was enlarged, whereas the Th17, but not Th1 percentage, was significantly decreased comparing with the vehicle-treated groups. Finally, both BrdU incorporation and in vitro Treg differentiation assays revealed that SM934 treatment could directly promote the expansion of Treg cells in vivo and in vitro. Conclusion: Taken together, this study demonstrated that SM934 treatment could ameliorate the murine EAE disease, which might be mediated by inducing Treg differentiation and expansion.
资助项目	National Science Fair Committee (NSFC), China[81072652] ; National Science Fair Committee (NSFC), China[81273524] ; National Science Fair Committee (NSFC), China[81273525] ; National Science & Technology Major Project "New Drug Creation and Manufacturing Program'', China[2012ZX09102-101-006] ; Science 1/4dagger Technology Commission of Shanghai Municipality, China[11431921102]
WOS关键词	CENTRAL-NERVOUS-SYSTEM ; MEDIATED SUPPRESSION ; CHEMOKINE RECEPTORS ; IL-17 PRODUCTION ; CUTTING EDGE ; TH17 CELLS ; INFLAMMATION ; DISEASE ; MICE ; INDUCTION
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000323734600081
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277496]
专题	药理学第一研究室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	Tang, Wei
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Lab Immunopharmacol, Shanghai 200031, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Li, Xin,Li, Tian-Tian,Zhang, Xiao-Hui,et al. Artemisinin Analogue SM934 Ameliorates Murine Experimental Autoimmune Encephalomyelitis through Enhancing the Expansion and Functions of Regulatory T Cell[J]. PLOS ONE,2013,8(8).
APA	Li, Xin.,Li, Tian-Tian.,Zhang, Xiao-Hui.,Hou, Li-Fei.,Yang, Xiao-Qian.,...&Zuo, Jian-Ping.(2013).Artemisinin Analogue SM934 Ameliorates Murine Experimental Autoimmune Encephalomyelitis through Enhancing the Expansion and Functions of Regulatory T Cell.PLOS ONE,8(8).
MLA	Li, Xin,et al."Artemisinin Analogue SM934 Ameliorates Murine Experimental Autoimmune Encephalomyelitis through Enhancing the Expansion and Functions of Regulatory T Cell".PLOS ONE 8.8(2013).