Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis
Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis
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姜黄素可恢复 M1 巨噬细胞中胆固醇转运稳态和炎症反应，预防动脉粥样硬化
DOI：
10.1016/j.bbrc.2015.10.051
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发表时间：
2015-11-27
影响因子：
3.1
通讯作者：
Yuan, Zu-Yi
中科院分区：
文献类型：
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作者：
Chen, Fang-Yuan;Zhou, Juan;Yuan, Zu-Yi
动脉壁脂蛋白胆固醇代谢障碍是动脉粥样硬化的主要原因，过量的脂质摄入和胆固醇稳态失调可加速动脉粥样硬化的发生。姜黄素通过缓解炎症、高脂血症和动脉粥样硬化发挥多种作用;然而，其在胆固醇转运稳态中的作用及其对炎性M1巨噬细胞的潜在影响知之甚少。本研究旨在探讨姜黄素对M1巨噬细胞胆固醇转运、炎症反应和细胞凋亡的影响。用LPS加IFN-γ诱导RAW264.7巨噬细胞（MO）12小时以形成M1亚型，然后在存在或不存在oxLDL的情况下与不同浓度（6.25和12.5 μ mol/L）的姜黄素孵育。然后，评价胆固醇流入/流出和泡沫细胞形成以及炎症和凋亡。结果发现，姜黄素增加胆固醇摄取的Dil-oxLDL结合测定，并同时增加胆固醇流出进行Apo-A1和HDL在M1细胞。姜黄素进一步加强ox-LDL诱导的胆固醇酯化和泡沫细胞形成所确定的油红0和BODIPY染色。此外，姜黄素显着减少ox-LDL诱导的细胞因子的产生，如IL-1 β，IL-6以及TNF-α和M1细胞凋亡。我们还发现姜黄素上调M1巨噬细胞中的CD36和ABCA 1。姜黄素增加了PPAR γ的表达，进而促进了CD36和ABCA 1的表达。总之，姜黄素可以增加M1巨噬细胞处理有害脂质的能力，从而促进脂质加工、处置和清除，这可能支持胆固醇稳态并发挥抗动脉粥样硬化作用。(C)2015 Elsevier Inc. All rights reserved.
Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (MO) were induced with LPS plus IFN-gamma for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 mu mol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red 0 and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1 beta, IL-6 as well as TNF-alpha and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPAR gamma expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect. (C) 2015 Elsevier Inc. All rights reserved.