therapeuticeffectsofdz2002areversiblesahhinhibitoronlupuspronenzbnzwf1miceviainterferencewithtlrmediatedapcresponse
文献类型：期刊论文
| 作者 | He Shijun1 ; Lin Zemin2; Wu Yanwei1; Bai Bingxin2; Yang Xiaoqian1; He Peilan1; Zhu Fenghua1; Tang Wei1; Zuo Jianping1
|
| 刊名 | actapharmacologicasinica
 |
| 出版日期 | 2014 |
| 卷号 | 35期号:2页码:219 |
| 关键词 | SAHH inhibitor Toll-like receptor signaling antigen-presenting cell systemic lupus erythematosus |
| ISSN号 | 1671-4083 |
| 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 NZB×NZW 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-β. In ex vivo studies, treatment of the mice with DZ2002 suppressed the development of pathogenic Th17 cells, significantly decreased IL-17, TGF-β, IL-6, and IL-23p19 production and impeded activation of the STAT3 protein and JNK/NF-κB signaling in splenocytes. DZ2002 (500 μmol/L) significantly suppressed TLR agonists-stimulated up-regulation in IL-6, IL-12p40, TNF-α, and IgG and IgM secretion as well as in HLA-DR and CD40 expression of dendritic cells among human PBMCs in vitro. DZ2002 (100 μmol/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. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/285538]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.中国科学院上海药物研究所 2.上海中医药大学 |
| 推荐引用方式 GB/T 7714 | He Shijun,Lin Zemin,Wu Yanwei,et al. therapeuticeffectsofdz2002areversiblesahhinhibitoronlupuspronenzbnzwf1miceviainterferencewithtlrmediatedapcresponse[J]. actapharmacologicasinica,2014,35(2):219. |
| APA | He Shijun.,Lin Zemin.,Wu Yanwei.,Bai Bingxin.,Yang Xiaoqian.,...&Zuo Jianping.(2014).therapeuticeffectsofdz2002areversiblesahhinhibitoronlupuspronenzbnzwf1miceviainterferencewithtlrmediatedapcresponse.actapharmacologicasinica,35(2),219. |
| MLA | He Shijun,et al."therapeuticeffectsofdz2002areversiblesahhinhibitoronlupuspronenzbnzwf1miceviainterferencewithtlrmediatedapcresponse".actapharmacologicasinica 35.2(2014):219. |
入库方式： OAI收割
来源：上海药物研究所
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