当前位置: X-MOL 学术Inflammation › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Electronegative LDL Induces M1 Polarization of Human Macrophages Through a LOX-1-Dependent Pathway.
Inflammation ( IF 5.1 ) Pub Date : 2020-05-11 , DOI: 10.1007/s10753-020-01229-6
Shwu-Fen Chang , Po-Yuan Chang , Yuan-Chun Chou , Shao-Chun Lu

In response to environmental stimuli, monocytes undergo polarization into classically activated (M1) or alternatively activated (M2) states. M1 and M2 macrophages exert opposing pro- and anti-inflammatory properties, respectively. Electronegative low-density lipoprotein (LDL) (LDL(-)) is a naturally occurring mildly oxidized LDL found in the plasma of patients with hypercholesterolemia, diabetes, and acute myocardial infarction, and has been shown to involve in the pathogenesis of atherosclerosis. In this study, we examined the effects of LDL(-) on macrophage polarization and the involvement of lectin-like oxidized LDL receptor-1 (LOX-1) in this process. THP-1 macrophages were treated with native LDL (nLDL) or LDL(-), and then the expression of M1/M2-related surface markers and cytokines were evaluated. The results show that treatment with LDL(-) resulted in profound increase in proinflammatory cytokines, IL-1β, IL-6, and TNF-α, and M1-surface marker CD86; however, M2-related cytokines, IL-10 and TGF-β, and M2-surface marker CD206 were not changed by LDL(-). Untreated or nLDL-treated cells were used as control. LDL(-)-induced M1 polarization and secretion of proinflammatory cytokines were diminished in LOX-1 knockdown cells. Taken together, the results show that LDL(-) promotes differentiation of human monocytes to M1 macrophages through a LOX-1-dependent pathway, and explore the contribution of LDL(-) and LOX-1 to the development of chronic inflammation in atherosclerosis.

中文翻译:

电负性 LDL 通过 LOX-1 依赖性途径诱导人类巨噬细胞的 M1 极化。

响应环境刺激,单核细胞经历极化进入经典激活 (M1) 或交替激活 (M2) 状态。M1 和 M2 巨噬细胞分别发挥相反的促炎和抗炎特性。电负性低密度脂蛋白 (LDL) (LDL(-)) 是一种天然存在的轻度氧化 LDL,存在于患有高胆固醇血症、糖尿病和急性心肌梗塞的患者的血浆中,已被证明与动脉粥样硬化的发病机制有关。在这项研究中,我们检查了 LDL(-) 对巨噬细胞极化的影响以及凝集素样氧化 LDL 受体 1 (LOX-1) 在此过程中的参与。THP-1 巨噬细胞用天然 LDL (nLDL) 或 LDL(-) 治疗,然后评估 M1/M2 相关表面标志物和细胞因子的表达。结果表明,用 LDL(-) 治疗导致促炎细胞因子、IL-1β、IL-6 和 TNF-α 以及 M1 表面标志物 CD86 显着增加;然而,与 M2 相关的细胞因子、IL-10 和 TGF-β,以及 M2 表面标志物 CD206 并没有被 LDL(-) 改变。未处理或 nLDL 处理的细胞用作对照。在 LOX-1 敲低细胞中,LDL(-) 诱导的 M1 极化和促炎细胞因子的分泌减少。综上所述,结果表明LDL(-)通过LOX-1依赖性途径促进人单核细胞向M1巨噬细胞分化,并探讨了LDL(-)和LOX-1对动脉粥样硬化慢性炎症发展的贡献。和 M2 表面标记 CD206 没有被 LDL(-) 改变。未处理或 nLDL 处理的细胞用作对照。在 LOX-1 敲低细胞中,LDL(-) 诱导的 M1 极化和促炎细胞因子的分泌减少。综上所述,结果表明LDL(-)通过LOX-1依赖性途径促进人单核细胞向M1巨噬细胞分化,并探讨了LDL(-)和LOX-1对动脉粥样硬化慢性炎症发展的贡献。和 M2 表面标记 CD206 没有被 LDL(-) 改变。未处理或 nLDL 处理的细胞用作对照。在 LOX-1 敲低细胞中,LDL(-) 诱导的 M1 极化和促炎细胞因子的分泌减少。综上所述,结果表明LDL(-)通过LOX-1依赖性途径促进人单核细胞向M1巨噬细胞分化,并探讨了LDL(-)和LOX-1对动脉粥样硬化慢性炎症发展的贡献。
更新日期:2020-05-11
down
wechat
bug