Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line.
Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line.
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在源自人外周单核细胞和 THP-1 单核细胞系的巨噬细胞中，IL-6 对 A 类巨噬细胞清道夫受体的转录抑制作用。
DOI：
10.1161/01.atv.19.8.1872
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Geng,YJ
中科院分区：
文献类型：
--
作者：
Liao,HS;Matsumoto,A;Itakura,H;Doi,T;Honda,M;Kodama,T;Geng,YJ
- A类巨噬细胞清道夫受体（MSR）的表达有助于巨噬细胞摄取修饰的低密度脂蛋白（LDL），并将这些细胞转化为载脂泡沫细胞，这是动脉粥样硬化的特征。许多环境因素，特别是促炎细胞因子和生长因子，可以对MSR表达产生调节作用，而胆固醇本身的细胞内积累不会在任何相当程度上影响MSR水平。在本研究中，通过使用体外模型，我们研究了是否与白细胞介素-6（IL-6），免疫调节，多潜能细胞因子的刺激，调节巨噬细胞中的MSR的表达和活动。当用IL-6处理时，来自外周单核细胞和佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）分化的THP-1单核细胞的巨噬细胞显示出MSR配体乙酰化LDL的摄取和/或结合显著降低。这种作用被MSR蛋白和mRNA表达的减少所抵消。用MSR启动子-报告基因构建体转染的THP-1细胞中的MSR启动子活性的分析表明，IL-6处理的THP-1巨噬细胞中的MSR启动子活性降低。电泳迁移率凝胶位移分析也显示了在IL-6处理的细胞中，转录因子与MSR启动子AP-1/ets元件的结合减少。因此，暴露于IL-6可以在转录水平上抑制分化的巨噬细胞中A类MSR的表达。这一结果表明，这种细胞因子可以调节动脉粥样硬化形成过程中泡沫细胞的形成。
—Expression of the class A macrophage scavenger receptor (MSR) contributes to the uptake of modified low density lipoproteins (LDL) by macrophages and transformation of these cells into lipid-laden foam cells, which characterize atherosclerosis. Many environmental factors, in particular, proinflammatory cytokines and growth factors, can exert regulatory effects on MSR expression, whereas intracellular accumulation of cholesterol itself does not influence MSR levels to any considerable extent. In the present study, by using an in vitro model, we examined whether stimulation with interleukin-6 (IL-6), an immunoregulatory, multipotential cytokine, modulates the expression and activities of the MSR in macrophages. When treated with IL-6, macrophages derived from peripheral monocytes and phorbol 12-myristate 13-acetate (PMA)–differentiated THP-1 monocytic cells showed significantly reduced uptake and/or binding of the MSR ligand, acetylated LDL. This effect was paralleled by a reduction in the expression of MSR protein and mRNA. Analysis of MSR promoter activity in THP-1 cells transfected with an MSR promoter–reporter gene construct demonstrated decreased activity of the MSR promoter in IL-6–treated THP-1 macrophages. Electrophoretic mobility gel shift assay also showed a reduction in the binding of a transcription factor to the MSR promoter AP-1/ets elements in IL-6–treated cells. Thus, exposure to IL-6 may inhibit expression of the class A MSR in differentiated macrophages at transcriptional levels. This result suggests that this cytokine may modulate foam cell formation during atherogenesis.