(5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells

doi:10.1016/j.intimp.2008.09.014

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

	(5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells
	Zhou, Ru 3; Tang, Wei3 ; He, Pei-Lan 3; Yang, Yi-Fu 3; Li, Yuan-Chao 1; Zuo, Jian-Ping2,3
刊名	INTERNATIONAL IMMUNOPHARMACOLOGY
	2009-01
卷号	9 期号:1 页码:63-69
关键词	(5R)-5-hydroxytriptolide Cytokine MAPK PBMC
ISSN号	1567-5769
DOI	10.1016/j.intimp.2008.09.014
文献子类	Article
英文摘要	Aim: (5R)-5-hydroxytriptolide (LLDT-8) displayed immunosuppressive activities both in vitro and in autoimmune disease models. Here, we aim to further clarify the effect of LLDT-8 on the immune responses of human peripheral blood mononuclear cells (PBMC). Method: Cell proliferation of human PBMC from healthy donors was evaluated by [H-3]-thymidine uptake. NK cell cytotoxicity was assayed using K562 cells in a 13 HI lysis assay. Cytokine production was determined by enzyme-linked immunosorbent assay. The expression of cell surface molecules was detected with flow cytometry. The mRNA expression and the protein phosphorylation levels were detected by RT-PCR and Western inimunoblot assay. Results: LLDT-8 at 25 and 50 nM significantly inhibited the PHA- and recall antigens-induced T cell proliferation, and Suppressed mixed lymphocyte reaction. LLDT-8 reduced cytokines production (IFN-gamma, IL-2, TNF-alpha) in PHA- and Sac-activated PBMC. LLDT-8 did not alter the increased expression of MHC class I/II and B7.1, but reduced B7.2 by approximately 30%. No effect of LLDT-8 was observed for the expression of T cell activation markers (CD69, CD154). However, LLDT-8 significantly reduced IFN-gamma-expressing T cell percentages and IFN-gamma mRNA transcription in PHA-activated T cells. It also inhibited the phosphorylation levels of JNK and p38. LLDT-8 did not affect NK cytotoxic activity against K562 cells. Conclusion: LLDT-8 was a promising immunosuppressant for human immune-related diseases. (C) 2008 Published by Elsevier B.V.
资助项目	Shanghai Science and Technology Committee[064319014] ; Shanghai Science and Technology Committee[074319110]
WOS关键词	NATURAL-KILLER-CELLS ; T-CELLS ; MAP KINASES ; ANTIGEN RECEPTOR ; IN-VITRO ; LLDT-8 ; JNK ; EXPRESSION ; MICE ; DIFFERENTIATION
WOS研究方向	Immunology ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000263144300009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279387]
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	Zuo, Jian-Ping
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Lab, State Key Lab Drug Res,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Zhou, Ru,Tang, Wei,He, Pei-Lan,et al. (5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2009,9(1):63-69.
APA	Zhou, Ru,Tang, Wei,He, Pei-Lan,Yang, Yi-Fu,Li, Yuan-Chao,&Zuo, Jian-Ping.(2009).(5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells.INTERNATIONAL IMMUNOPHARMACOLOGY,9(1),63-69.
MLA	Zhou, Ru,et al."(5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells".INTERNATIONAL IMMUNOPHARMACOLOGY 9.1(2009):63-69.