Browsing by Author "Hu, Yuan"

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    The persistence of low-grade inflammatory monocytes contributes to aggravated Atherosclerosis
    Geng, Shuo; Chen, Keqiang; Yuan, Ruoxi; Maitra, Urmila; Na, Diao; Chen, Chun; Zhang, Yao; Li, Liwu; Xiong, Huabao; Peng, Liang; Hu, Yuan; Qi, Chen-Feng; Pierce, Susan; Ling, Wenhua (Nature, 2016-11-08)
    Sustained low-grade inflammation mediated by non-resolving inflammatory monocytes has long been suspected in the pathogenesis of atherosclerosis; however, the molecular mechanisms responsible for the sustainment of non-resolving inflammatory monocytes during atherosclerosis are poorly understood. Here we observe that subclinical endotoxemia, often seen in humans with chronic inflammation, aggravates murine atherosclerosis through programming monocytes into a non-resolving inflammatory state with elevated Ly6C, CCR5, MCP-1 and reduced SR-B1. The sustainment of inflammatory monocytes is due to the disruption of homeostatic tolerance through the elevation of miR-24 and reduction of the key negative-feedback regulator IRAK-M. miR-24 reduces the levels of Smad4 required for the expression of IRAK-M and also downregulates key lipid-processing molecule SR-B1. IRAK-M deficiency in turn leads to elevated miR-24 levels, sustains disruption of monocyte homeostasis and aggravates atherosclerosis. Our data define an integrated feedback circuit in monocytes and its disruption may lead to non-resolving low-grade inflammation conducive to atherosclerosis.
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    Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5
    Peng, Liang; Zhang, Hui; Hao, Yuanyuan; Xu, Feihong; Yang, Jianjun; Zhang, Ruihua; Lu, Geming; Zheng, Zihan; Cui, Miao; Qi, Chen-Feng; Chen, Chun; Wang, Juan; Hu, Yuan; Wang, Di; Pierce, Susan; Li, Liwu; Xiong, Huabao (2016-12)
    The regulation of macrophage orientation pathological conditions is important but still incompletely understood. Here, we show that IL-10 and Rag1 double knockout mice spontaneously develop colitis with dominant M1 macrophage phenotype, suggesting that IL-10 regulates macrophage orientation in inflammation. We demonstrate that IL-10 stimulation induced miR-146b expression, and that the expression of miR-146b was impaired in IL-10 deficient macrophages. Our data show that miR-146b targets IRF5, resulting in the regulation of macrophage activation. Furthermore, miR-146b deficient mice developed intestinal inflammation with enhanced M1 macrophage polarization. Finally, miR-146b mimic treatment significantly suppresses M1 macrophage activation and ameliorates colitis development in vivo. Collectively, the results suggest that IL-10 dependent miR-146b plays an important role in the modulation of M1 macrophage orientation. (C) 2016 The Authors. Published by Elsevier B.V.