Interleukin-36γ aggravates macrophage foam cell formation and atherosclerosis progression in ApoE knockout mice
Interleukin-36γ aggravates macrophage foam cell formation and atherosclerosis progression in ApoE knockout mice
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Interleukin-36 gamma 加剧 ApoE 敲除小鼠巨噬细胞泡沫细胞形成和动脉粥样硬化进展
DOI：
10.1016/j.cyto.2021.155630
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发表时间：
2021-07-07
期刊：
影响因子：
3.8
通讯作者：
Fan, Jiao
中科院分区：
文献类型：
--
作者：
Zhang, Minghua;Liu, Jing;Fan, Jiao
动脉粥样硬化相关的心血管疾病是全世界死亡的主要原因。巨噬细胞衍生的泡沫细胞形成是动脉粥样硬化形成的关键早期事件。然而，参与这种疾病的分子途径尚未完全阐明。白介素（IL）-36在炎症中发挥着至关重要的作用，本研究旨在探讨IL-36γ在动脉粥样硬化的发病机制和调节中的可能作用。在这项研究中，我们发现IL-36γ调节巨噬细胞中的炎症反应和脂蛋白代谢过程，并通过增加巨噬细胞泡沫细胞的形成和氧化低密度脂蛋白的摄取来发挥其促进动脉粥样硬化的作用。从机制上讲，IL-36 γ 通过巨噬细胞中的磷酸肌醇 3 激酶途径特异性上调清道夫受体 CD36 的表达。这些结果有助于我们理解 IL-36 γ 作为泡沫细胞形成和动脉粥样硬化进展的新型调节剂。
Atherosclerosis-related cardiovascular diseases are the leading cause of mortality worldwide. Macrophagederived foam cell formation is a critical early event in atherogenesis. However, the molecular pathways involved in this disease have not been fully elucidated. Interleukin (IL)-36 plays a crucial role in inflammation, and this study was conducted to investigate the possible role of IL-36 gamma in the pathogenesis and regulation of atherosclerosis. In this study, we show that IL-36 gamma regulates inflammatory responses and lipoprotein metabolic processes in macrophages and exerts its atherosclerosis-promoting effects by increasing macrophage foam cell formation and uptake of oxidized low-density lipoproteins. Mechanistically, IL-36 gamma specifically upregulates expression of the scavenger receptor CD36 through the phosphoinositide 3-kinase pathway in macrophages. These results contribute to our understanding of IL-36 gamma as a novel regulator of foam cell formation and atherogenesis progression.