Silencing LAIR-1 in human THP-1 macrophage increases foam cell formation by modulating PPARγ and M2 polarization

沉默人类 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

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作者:Xin Yi, Jinxue Zhang, Ran Zhuang, Song Wang, Shiyang Cheng, Dongliang Zhang, Jiangang Xie, Wei Hu, Xueqin Liu, Yun Zhang, Yong Ding, Yuan Zhang

Abstract

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.

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