C1q/TNF-related protein 1 links macrophage lipid metabolism to inflammation and atherosclerosis
C1q/TNF-related protein 1 links macrophage lipid metabolism to inflammation and atherosclerosis
复制标题
C1q/TNF相关蛋白1将巨噬细胞脂质代谢与炎症和动脉粥样硬化联系起来
DOI：
10.1016/j.atherosclerosis.2016.04.024
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发表时间：
2016-07-01
期刊：
影响因子：
5.3
通讯作者：
Shen, Wei Feng
中科院分区：
文献类型：
--
作者：
Wang, Xiao Qun;Liu, Zhu Hui;Shen, Wei Feng
背景和目的：巨噬细胞通过摄取沉积的脂蛋白并引发局部炎症，是动脉粥样硬化发生发展的主要因素。以前，我们和其他人已经证明了C1q/肿瘤坏死因子相关蛋白(CTRPs)在血管功能中发挥着不同的作用。本研究旨在探讨巨噬细胞重要生物学过程中CTRP表达水平的变化及其与炎症反应的关系。方法：采用Western印迹和实时荧光定量聚合酶链式反应技术分析人外周血单个核细胞、原代巨噬细胞和高脂泡沫细胞中CTRPs的表达水平。通过生物信息学分析和染色质免疫沉淀进一步研究了调控CTPR1表达的机制。结果：原代培养的人巨噬细胞向外周血单核细胞分化后，几乎所有的CTRPs均明显升高。特别是，CTRP1在暴露于氧化型低密度脂蛋白(OxLDL)时以依赖于过氧化物酶体增殖物激活受体(PPAR)的方式进一步上调。染色质免疫沉淀也证实了oxLDL处理后CTRP1启动子中存在PPAR-γ。刺激CTRP1后，巨噬细胞中MCP-1、TNF-α、IL-1β和IL-6等促动脉粥样硬化因子的分泌明显增加，而用CTRP1中和抗体处理后，oxLDL诱导的炎性细胞因子的产生明显减弱。结论：CTRP1在连接巨噬细胞脂代谢紊乱和炎症反应中起重要作用。(C)2016爱思唯尔爱尔兰有限公司。保留所有权利。
Background and aims: Macrophage is a major contributor to the development of atherosclerosis by taking up deposited lipoprotein and eliciting local inflammation. Previously, we and others have shown C1q/TNF-related proteins (CTRPs) play diverse roles in vascular functions. In this study, we sought to investigate the changes in CTRP expression levels during vital biological processes in macrophages and their relation to inflammatory responses.Methods: Western blot and real-time PCR were performed to analyze CTRPs expression levels in human peripheral blood mononuclear cells, primary macrophages and lipid-laden foam cells. Mechanisms that regulate CTPR1 expression were further investigated by bioinformatic analysis and chromatin immunoprecipitation. Enzyme-linked immunosorbent assay was performed to measure the concentration of inflammatory cytokines.Results: We found that almost all CTRPs were significantly increased in primary human macrophages after differentiation from peripheral blood mononuclear cells. In particular, CTRP1 was further up-regulated upon exposure to oxidized low-density lipoprotein (oxLDL) in a peroxisome proliferator-activated receptor (PPAR)-dependent manner. Chromatin immunoprecipitation also confirmed the presence of PPAR-gamma in the CTRP1 promoter after oxLDL treatment. Stimulation of CTRP1 led to markedly enhanced secretion of pro-atherogenic factors, including MCP-1, TNF-alpha, IL-1 beta, and IL-6, whereas oxLDL-induced inflammatory cytokine production was significantly attenuated after the treatment with CTRP1 neutralizing antibody.Conclusions: These data suggest an essential role of CTRP1 in linking dysregulation of lipid metabolism and inflammatory responses in macrophages. (C) 2016 Elsevier Ireland Ltd. All rights reserved.