中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 药理学第一研究室
Therapeutic effects of DZ2002, a reversible SAHH inhibitor, on lupus-prone NZBxNZW F1 mice via interference with TLR-mediated APC response

文献类型：期刊论文

作者He, Shi-jun1; Lin, Ze-min2; Wu, Yan-wei1; Bai, Bing-xin2; Yang, Xiao-qian1; He, Pei-lan1; Zhu, Feng-hua1; Tang, Wei1; Zuo, Jian-ping1,2
刊名ACTA PHARMACOLOGICA SINICA
出版日期2014-02
卷号35期号:2页码:219-229
关键词SAHH inhibitor Toll-like receptor signaling antigen-presenting cell systemic lupus erythematosus
ISSN号1671-4083
DOI10.1038/aps.2013.167
文献子类Article
英文摘要Aim: To examine the therapeutic effects and underlying mechanisms of DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, on lupus-prone female NZBxNZW F1 (NZB/W F1) mice. Methods: Female NZB/W F1 mice were treated orally with DZ2002 (0.5 mg.kg(-1).d(-1)) for 11 weeks, and the proteinuria level and body weight were monitored. After the mice ware euthanized, serum biochemical parameters and renal damage were determined. Splenocytes of NZB/W F1 mice were isolated for ex vivo study. Toll-like receptor (TLR)-stimulated human peripheral blood mononuclear cells (PBMCs) or murine bone marrow-derived dendritic cells (BMDCs) were used for in vitro study. Results: Treatment of the mice with DZ2002 significantly attenuated the progression of glomerulonephritis and improved the overall health. The improvement was accompanied by decreased levels of nephritogenic anti-dsDNA IgG2a and IgG3 antibodies, serum IL-17, IL-23p19 and TGF-beta. In ex vivo studies, treatment of the mice with DZ2002 suppressed the development of pathogenic Th17 cells, significantly decreased IL-17, TGF-beta, IL-6, and IL-23p19 production and impeded activation of the STAT3 protein and JNK/NF-kappa B signaling in splenocytes. DZ2002 (500 mu mol/L) significantly suppressed TLR agonists-stimulated up-regulation in IL-6, IL-12p40, TNF-alpha, and IgG and IgM secretion as well as in HLA-DR and CD40 expression of dendritic cells among human PBMCs in vitro. DZ2002 (100 mu mol/L) also significantly suppressed TLR agonists-stimulated up-regulation in IL-6 and IL-23p19 production in murine BMDCs, and prevented Th17 differentiation and suppressed IL-17 secretion by the T cells in a BMDC-T cell co-culture system. Conclusion: DZ2002 effectively ameliorates lupus syndrome in NZB/W F1 mice by regulating TLR signaling-mediated antigen presenting cell (APC) responses.
WOS关键词L-HOMOCYSTEINE HYDROLASE ; GROWTH-FACTOR-BETA ; T-CELL-ACTIVATION ; DENDRITIC CELLS ; AUTOANTIBODY PRODUCTION ; AUTOIMMUNE-DISEASE ; INDUCED ARTHRITIS ; MURINE LUPUS ; IN-VITRO ; ERYTHEMATOSUS
资助项目National Natural Science Foundation of China (NSFC)[81072652] ; National Natural Science Foundation of China (NSFC)[81273524] ; National Natural Science Foundation of China (NSFC)[81273525] ; National Science & Technology Major Project "New Drug Creation and Manufacturing Program", China[2012ZX09102-101-006] ; Science & Technology Commission of Shanghai Municipality, China[11431921102]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
CSCD记录号CSCD:5040828
WOS记录号WOS:000330581300007
出版者ACTA PHARMACOLOGICA SINICA
源URL[http://119.78.100.183/handle/2S10ELR8/277211]  
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 201203, Peoples R China;
2.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 He, Shi-jun,Lin, Ze-min,Wu, Yan-wei,et al. Therapeutic effects of DZ2002, a reversible SAHH inhibitor, on lupus-prone NZBxNZW F1 mice via interference with TLR-mediated APC response[J]. ACTA PHARMACOLOGICA SINICA,2014,35(2):219-229.
APA He, Shi-jun.,Lin, Ze-min.,Wu, Yan-wei.,Bai, Bing-xin.,Yang, Xiao-qian.,...&Zuo, Jian-ping.(2014).Therapeutic effects of DZ2002, a reversible SAHH inhibitor, on lupus-prone NZBxNZW F1 mice via interference with TLR-mediated APC response.ACTA PHARMACOLOGICA SINICA,35(2),219-229.
MLA He, Shi-jun,et al."Therapeutic effects of DZ2002, a reversible SAHH inhibitor, on lupus-prone NZBxNZW F1 mice via interference with TLR-mediated APC response".ACTA PHARMACOLOGICA SINICA 35.2(2014):219-229.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。