Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening
文献类型：期刊论文
| 作者 | Chen, Shuai2; Zhou, Jinfeng2; Cai, Yingying2; Zheng, Xinyuan2; Xie, Sirong2; Liao, Yuhan2; Zhu, Yu2; Qin, Chaoyan2; Lai, Weiming2; Yang, Cuixia2 |
| 刊名 | SCIENTIFIC REPORTS
 |
| 出版日期 | 2017-03-08 |
| 卷号 | 7 |
| ISSN号 | 2045-2322 |
| DOI | 10.1038/srep43820 |
| 文献子类 | Article |
| 英文摘要 | Dendritic cells (DCs) play a critical role in the pathogenesis of autoimmune diseases including multiple sclerosis, and targeting DCs' cytokines production is an important strategy for autoimmune diseases treatment. By establishing a high-throughput screening system, we analyzed LOPAC drug library to identify drugs that control the secretion of IL-6 by DCs, we selected the most likely candidate drug, BVDU, and found that it affected not only IL-6 production, but also that of IL-12, IL-1 beta during the DCs differentiation and maturation. The mechanism studies showed that BVDU treatment restricted the phosphorylation of MAP kinase, which played an important role in DC cytokine production. We further assessed the in vivo therapeutic potentials of BVDU on mouse models including EAE and STZ-induced T1D, and found that BVDU treated EAE mice exhibited significantly lower EAE clinical scores, decreased leukocyte infiltration in central nervous system lesions, and reduced demyelination. As in T1D mice, BVDU treatment also showed promising therapeutic effects based on both alleviated disease symptoms and tissue pathogenesis. More interestingly, the modulating effect of BVDU on IL-6 production was further verified in human primary DCs. The above data supported the promising application of our screen model, and also the potential of BVDU for autoimmune diseases therapy. |
| WOS关键词 | CENTRAL-NERVOUS-SYSTEM ; MULTIPLE-SCLEROSIS ; T-CELLS ; GLIAL-CELLS ; ROR-GAMMA ; DIFFERENTIATION ; INTERLEUKIN-6 ; MATURATION ; ADENOSINE ; ENCEPHALOMYELITIS |
| 资助项目 | Ministry of Science and Technology of China[2014CB541903] ; Ministry of Science and Technology of China[2012CB910404] ; National Natural Science Foundation of China[31171348] ; National Natural Science Foundation of China[31371414] ; Shanghai Municipal Education Commission[14zz042] ; State Key Laboratory of Drug Research[SIMM1302KF-09] ; Fundamental Research Funds for the Central Universities[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000395687500001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272745]  |
| 专题 | 国家新药筛选中心 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 | Du, Changsheng |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Beijing 201203, Peoples R China; 2.Tongji Univ, Shanghai Tenth Peoples Hosp Tongji Univ, Sch Life Sci & Technol, Dept Cent Lab, Shanghai 200092, Peoples R China; 3.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, Shanghai 200092, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Shuai,Zhou, Jinfeng,Cai, Yingying,et al. Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening[J]. SCIENTIFIC REPORTS,2017,7. |
| APA | Chen, Shuai.,Zhou, Jinfeng.,Cai, Yingying.,Zheng, Xinyuan.,Xie, Sirong.,...&Du, Changsheng.(2017).Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening.SCIENTIFIC REPORTS,7. |
| MLA | Chen, Shuai,et al."Discovery of BVDU as a promising Drug for autoimmune diseases Therapy by Dendritic-cell-based functional screening".SCIENTIFIC REPORTS 7(2017). |
入库方式： OAI收割
来源：上海药物研究所
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