Identification of a Lysosomal Pathway That Modulates Glucocorticoid Signaling and the Inflammatory Response
文献类型：期刊论文
| 作者 | He, Yuanzheng1; Xu, Yong1; Zhang, Chenghai1; Gao, Xiang1; Dykema, Karl J.5; Martin, Katie R.6; Ke, Jiyuan1; Hudson, Eric A.3; Khoo, Sok Kean2,3; Resau, James H.3 |
| 刊名 | SCIENCE SIGNALING
 |
| 出版日期 | 2011-07-05 |
| 卷号 | 4期号:180 |
| ISSN号 | 1945-0877 |
| DOI | 10.1126/scisignal.2001450 |
| 文献子类 | Article |
| 英文摘要 | The antimalaria drug chloroquine has been used as an anti-inflammatory agent for treating systemic lupus erythematosus and rheumatoid arthritis. We report that chloroquine promoted the transrepression of proinflammatory cytokines by the glucocorticoid receptor (GR). In a mouse collagen-induced arthritis model, chloroquine enhanced the therapeutic effects of glucocorticoid treatment. By inhibiting lysosome function, chloroquine synergistically activated glucocorticoid signaling. Lysosomal inhibition by either bafilomycin A1 (an inhibitor of the vacuolar adenosine triphosphatase) or knockdown of transcription factor EB (TFEB, a master activator of lysosomal biogenesis) mimicked the effects of chloroquine. The abundance of the GR, as well as that of the androgen receptor and estrogen receptor, correlated with changes in lysosomal biogenesis. Thus, we showed that glucocorticoid signaling is regulated by lysosomes, which provides a mechanistic basis for treating inflammation and autoimmune diseases with a combination of glucocorticoids and lysosomal inhibitors. |
| WOS关键词 | RHEUMATOID-ARTHRITIS ; RANDOMIZED-TRIAL ; AUTOPHAGY ; RECEPTOR ; CHLOROQUINE ; MECHANISMS ; PROTEIN ; THERAPY ; HORMONE ; DISEASE |
| 资助项目 | NIDDK/NIH[DK066202] ; NIDDK/NIH[DK071662] ; American Asthma Foundation[00000000] ; Department of Defense of the Office of Congressionally Directed Medical Research Programs[PC081089] ; Jay and Betty Van Andel Foundation[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000292381100002 |
| 出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278478]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | He, Yuanzheng |
| 作者单位 | 1.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA; 2.Van Andel Res Inst, Lab Microarray Technol, Grand Rapids, MI 49503 USA; 3.Van Andel Res Inst, Lab Analyt Cellular & Mol Microscopy, Grand Rapids, MI 49503 USA; 4.Chinese Acad Sci, VARI SIMM Ctr, Ctr Struct & Funct Drug Targets, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Van Andel Res Inst, Lab Computat Biol, Grand Rapids, MI 49503 USA; 6.Van Andel Res Inst, Lab Syst Biol, Grand Rapids, MI 49503 USA; 7.Van Andel Res Inst, Lab Cell Struct & Signal Integrat, Grand Rapids, MI 49503 USA; |
| 推荐引用方式 GB/T 7714 | He, Yuanzheng,Xu, Yong,Zhang, Chenghai,et al. Identification of a Lysosomal Pathway That Modulates Glucocorticoid Signaling and the Inflammatory Response[J]. SCIENCE SIGNALING,2011,4(180). |
| APA | He, Yuanzheng.,Xu, Yong.,Zhang, Chenghai.,Gao, Xiang.,Dykema, Karl J..,...&Xu, H. Eric.(2011).Identification of a Lysosomal Pathway That Modulates Glucocorticoid Signaling and the Inflammatory Response.SCIENCE SIGNALING,4(180). |
| MLA | He, Yuanzheng,et al."Identification of a Lysosomal Pathway That Modulates Glucocorticoid Signaling and the Inflammatory Response".SCIENCE SIGNALING 4.180(2011). |
入库方式： OAI收割
来源：上海药物研究所
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