Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity

doi:10.1038/aps.2012.208

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	Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity
	Wan, Chun-ping 1,2; Gao, Li-xin 3; Hou, Li-fei 3; Yang, Xiao-qian 3; He, Pei-lan 3; Yang, Yi-fu 1; Tang, Wei3 ; Yue, Jian-min3 ; Li, Jia3 ; Zuo, Jian-ping1,3
刊名	ACTA PHARMACOLOGICA SINICA
	2013-04
卷号	34 期号:4 页码:522-530
关键词	immunomodulating agent Astragalus membranaceus Bge astragaloside II CD45 PTPase LCK T cell splenocyte Src-family kinase IFN-gamma IL-2 cyclophosphamide
ISSN号	1671-4083
DOI	10.1038/aps.2012.208
文献子类	Article
英文摘要	Aim: To investigate the immunomodulating activity of astragalosides, the active compounds from a traditional tonic herb Astragalus membranaceus Bge, and to explore the molecular mechanisms underlying the actions, focusing on CD45 protein tyrosine phosphatase (CD45 PTPase), which plays a critical role in T lymphocyte activation. Methods: Primary splenocytes and T cells were prepared from mice. CD45 PTPase activity was assessed using a colorimetric assay. Cell proliferation was measured using a [H-3]-thymidine incorporation assay. Cytokine proteins and mRNAs were examined with ELISA and RT-PCR, respectively. Activation markers, including CD25 and CD69, were analyzed using flow cytometry. Activation of LCK (Tyr505) was detected using Western blot analysis. Mice were injected with the immunosuppressant cyclophosphamide (CTX, 80 mg/kg), and administered astragaloside II (50 mg/kg). Results: Astragaloside I, II, III, and IV concentration-dependently increased the CD45-mediated of pNPP/OMFP hydrolysis with the EC50 values ranged from 3.33 to 10.42 mu g/mL. Astragaloside II (10 and 30 nmol/L) significantly enhanced the proliferation of primary splenocytes induced by ConA, alloantigen or anti-CD3. Astragaloside II (30 nmol/L) significantly increased IL-2 and IFN-gamma secretion, upregulated the mRNA levels of IFN-gamma and T-bet in primary splenocytes, and promoted CD25 and CD69 expression on primary CD4(+) T cells upon TCR stimulation. Furthermore, astragaloside II (100 nmol/L) promoted CD45-mediated dephosphorylation of LCK (Tyr505) in primary T cells, which could be blocked by a specific CD45 PTPase inhibitor. In CTX-induced immunosuppressed mice, oral administration of astragaloside II restored the proliferation of splenic T cells and the production of IFN-gamma and IL-2. However, astragaloside II had no apparent effects on B cell proliferation. Conclusion: Astragaloside II enhances T cell activation by regulating the activity of CD45 PTPase, which may explain why Astragalus membranaceus Bge is used as a tonic herb in treating immunosuppressive diseases.
资助项目	National Natural Science Foundation of China[81072652] ; National Natural Science Foundation of China[81273524] ; National Science & Technology Major Project "New Drug Creation and Manufacturing Program" China[2012ZX09102-101-006]
WOS关键词	IN-VITRO ; LYMPHOCYTE-ACTIVATION ; ECHINACEA-PURPUREA ; GLYCYRRHIZA-GLABRA ; EXPRESSION ; RESPONSES ; PROLIFERATION ; MEMBRANACEUS ; INHIBITORS ; SAPONINS
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:4796642
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000317106600011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277672]
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天然药物化学研究室药理学第一研究室
通讯作者	Yue, Jian-min
作者单位	1.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China; 2.Yunnan Univ Tradit Chinese Med, Affiliated Hosp 1, Cent Lab, Kunming 650021, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Wan, Chun-ping,Gao, Li-xin,Hou, Li-fei,et al. Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity[J]. ACTA PHARMACOLOGICA SINICA,2013,34(4):522-530.
APA	Wan, Chun-ping.,Gao, Li-xin.,Hou, Li-fei.,Yang, Xiao-qian.,He, Pei-lan.,...&Zuo, Jian-ping.(2013).Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity.ACTA PHARMACOLOGICA SINICA,34(4),522-530.
MLA	Wan, Chun-ping,et al."Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity".ACTA PHARMACOLOGICA SINICA 34.4(2013):522-530.