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DOI | 10.1126/science.aal3535 |
Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages | |
Ip, W. K. Eddie1,2; Hoshi, Namiko1,2,4; Shouval, Dror S.3,5,6; Snapper, Scott3; Medzhitov, Ruslan1,2 | |
2017-05-05 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 356期号:6337页码:513-519 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Japan; Israel |
英文摘要 | Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4. Consequently, IL-10 promotes mitophagy that eliminates dysfunctional mitochondria characterized by low membrane potential and a high level of reactive oxygen species. In the absence of IL-10 signaling, macrophages accumulate damaged mitochondria in a mouse model of colitis and inflammatory bowel disease patients, and this results in dysregulated activation of the NLRP3 inflammasome and production of IL-1 beta. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000400545700032 |
WOS关键词 | MECHANISTIC TARGET ; DENDRITIC CELLS ; GROWTH-CONTROL ; MTORC1 ; AUTOPHAGY ; INNATE ; INHIBITION ; COMMITMENT ; ACTIVATION ; IL-1-BETA |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/195980 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06510 USA; 2.Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA; 3.Harvard Med Sch, Boston Childrens Hosp, Boston, MA 02115 USA; 4.Kobe Univ, Div Gastroenterol, Grad Sch Med, Kobe, Hyogo, Japan; 5.Edmond & Lily Safra Childrens Hosp, Div Pediat Gastroenterol & Nutr, Sheba Med Ctr, Tel Hashomer, Israel; 6.Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel |
推荐引用方式 GB/T 7714 | Ip, W. K. Eddie,Hoshi, Namiko,Shouval, Dror S.,et al. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages[J]. SCIENCE,2017,356(6337):513-519. |
APA | Ip, W. K. Eddie,Hoshi, Namiko,Shouval, Dror S.,Snapper, Scott,&Medzhitov, Ruslan.(2017).Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages.SCIENCE,356(6337),513-519. |
MLA | Ip, W. K. Eddie,et al."Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages".SCIENCE 356.6337(2017):513-519. |
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