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

	Astragaloside Ⅱ triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity
	Wan Chunping 1; Gao Lixin 2; Hou Lifei 2; Yang Xiaoqian 2; He Peilan 2; Yang Yifu 1; Tang Wei 2; Yue Jianmin 2; Li Jia 2; Zuo Jianping 1
刊名	Acta Pharmacologica Sinica
	2013
卷号	34 期号:4 页码:522
关键词	immunomodulating agent Astragalus membranaceus Bge astragaloside II CD45 PTPase LCK T cell splenocyte Src-family kinase IFN-y IL-2 cyclophosphamide
ISSN号	1671-4083
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 3H-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 EC_(50) values ranged from 3.33 to 10.42 μg/mL. Astragaloside Ⅱ (10 and 30 μg/mL) significantly enhanced the proliferation of primary splenocytes induced by ConA, alloantigen or anti-CD3. Astragaloside II (30 pg/mL) significantly increased IL-2 and IFN-y secretion, upregulated the mRNA levels of IFN-y and T-bet in primary splenocytes, and promoted CD25 and CD69 expression on primary CD4* T cells upon TCR stimulation. Furthermore, astragaloside II (100 ng/mL) 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-y 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.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/293020]
专题	中国科学院上海药物研究所
作者单位	1.上海中医药大学 2.中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Wan Chunping,Gao Lixin,Hou Lifei,et al. Astragaloside Ⅱ triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity[J]. Acta Pharmacologica Sinica,2013,34(4):522.
APA	Wan Chunping.,Gao Lixin.,Hou Lifei.,Yang Xiaoqian.,He Peilan.,...&Zuo Jianping.(2013).Astragaloside Ⅱ triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity.Acta Pharmacologica Sinica,34(4),522.
MLA	Wan Chunping,et al."Astragaloside Ⅱ triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity".Acta Pharmacologica Sinica 34.4(2013):522.