Silencing LAIR-1 in human THP-1 macrophage increases foam cell formation by modulating PPAR gamma and M2 polarization
Silencing LAIR-1 in human THP-1 macrophage increases foam cell formation by modulating PPAR gamma and M2 polarization
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沉默人 THP-1 巨噬细胞中的 LAIR-1 通过调节 PPARγ 和 M2 极化来增加泡沫细胞的形成
DOI：
10.1016/j.cyto.2018.08.028
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发表时间：
2018
期刊：
影响因子：
3.8
通讯作者：
Zhang Yuan
中科院分区：
文献类型：
--
作者：
Yi Xin;Zhang Jinxue;Zhuang Ran;Wang Song;Cheng Shiyang;Zhang Dongliang;Xie Jiangang;Hu Wei;Liu Xueqin;Zhang Yun;Ding Yong;Zhang Yuan
巨噬细胞来源的泡沫细胞的形成可能标志着动脉粥样硬化的初始阶段。我们研究了巨噬细胞中白细胞相关免疫球蛋白样受体1(LAIR-1)的表达与泡沫细胞形成的关系。将THP-1来源的巨噬细胞和骨髓巨噬细胞与氧化型低密度脂蛋白(ox-LDL)孵育，建立泡沫细胞模型。通过油红O染色和Dil-ox-LDL荧光强度评价LAIR-1在泡沫细胞形成中的作用。采用定量聚合酶链式反应(QPCR法)检测PPARγ、胆固醇代谢相关基因以及LAIR-1在激活经典激活(M1)和交替激活(M2)巨噬细胞中的作用。免疫印迹法检测蛋白酪氨酸磷酸酶-1(SHP-1)和cAMP反应元件结合蛋白(CREB)的活性。结果表明，沉默巨噬细胞中的LAIR-1可以调节SHP-1/CREB/PPARγ通路，从而促进M2巨噬细胞极化，增加泡沫细胞的形成。因此，抑制巨噬细胞中的LAIR-1可能促进泡沫细胞的形成和动脉粥样硬化。
Formation of macrophage-derived foam cells may mark the initial stages of atherosclerosis. We investigated the association between the expression of the leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) in macrophages and foam cell formation. A foam cell model was established by incubating THP-1-derived macrophages and bone marrow macrophages (BMMs) with oxidized low-density lipoprotein (ox-LDL). The role of LAIR-1 in foam cell formation was evaluated via Oil Red O staining and Dil-ox-LDL fluorescence intensities. Peroxisome proliferator-activated receptor gamma (PPARγ), cholesterol metabolism-related genes, and the role of LAIR-1 in activating classically activated (M1) and alternatively activated (M2) macrophages were evaluated by qPCR. Additionally, activation of protein-tyrosine phosphatase-1 (SHP-1) and cAMP-response element binding protein (CREB) were detected by western blotting. Results indicated that silencing LAIR-1 in macrophages modulated the SHP-1/CREB/PPARγ pathway, thereby promoting M2 macrophage polarization and increasing foam cell formation. Therefore, Inhibition of LAIR-1 in macrophages may promote foam cell formation and atherosclerosis.