Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation
文献类型：期刊论文
| 作者 | Wu, Yanwei1; He, Shijun1 ; Bai, Bingxin2; Zhang, Luyao1; Xue, Lu2; Lin, Zemin2; Yang, Xiaoqian1; Zhu, Fenghua1; He, Peilan1; Tang, Wei1
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| 刊名 | CELLULAR & MOLECULAR IMMUNOLOGY
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| 出版日期 | 2016-05 |
| 卷号 | 13期号:3页码:379-390 |
| 关键词 | B cell plasma cell SM934 systemic lupus erythematosus Toll-like receptor |
| ISSN号 | 1672-7681 |
| DOI | 10.1038/cmi.2015.13 |
| 文献子类 | Article |
| 英文摘要 | We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRL/lpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus (SLE). When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/lpr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies (ANAs) and of the pathogenic cytokines IL-6, IL-10 and IL-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/lpr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell (PC) numbers. Ex vivo, SM934 suppressed the Toll-like receptor (TLR)-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-kappa B phosphorylation. In human peripheral blood mononuclear cells (PBMCs), consistent with the results in MRL/lpr mice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/lpr mice by suppressing B cell activation and plasma cell formation. |
| WOS关键词 | WILFORDII HOOK-F ; ETHYL-ACETATE EXTRACT ; TOLL-LIKE RECEPTORS ; SOMATIC HYPERMUTATION ; DISEASE PROGRESSION ; AUTOIMMUNE-DISEASE ; GERMINAL-CENTERS ; NZB/W F1-MICE ; MURINE MODEL ; ERYTHEMATOSUS |
| 资助项目 | National Science Fair Committee (NSFC), China[81273524] ; National Science Fair Committee (NSFC), China[81322049] ; National Science & Technology Major Project 'New Drug Creation and Manufacturing Program', China[2014ZX09101002] ; National Key Basic Research Programme (973 Programme)[2014CB541906] |
| WOS研究方向 | Immunology |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5700759 |
| WOS记录号 | WOS:000375416500012 |
| 出版者 | CHIN SOCIETY IMMUNOLOGY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276058]  |
| 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; Zuo, Jianping |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Lab Immunopharmacol, Shanghai 200031, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Yanwei,He, Shijun,Bai, Bingxin,et al. Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation[J]. CELLULAR & MOLECULAR IMMUNOLOGY,2016,13(3):379-390. |
| APA | Wu, Yanwei.,He, Shijun.,Bai, Bingxin.,Zhang, Luyao.,Xue, Lu.,...&Zuo, Jianping.(2016).Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation.CELLULAR & MOLECULAR IMMUNOLOGY,13(3),379-390. |
| MLA | Wu, Yanwei,et al."Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation".CELLULAR & MOLECULAR IMMUNOLOGY 13.3(2016):379-390. |
入库方式： OAI收割
来源：上海药物研究所
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