IL-6对THP-1巨噬细胞源性泡沫细胞ABCA1和ABCG1表达的影响及其机制研究

发布时间：2018-09-18 10:12

【摘要】： 目的:本研究旨在探讨白介素-6(IL-6)对THP-1巨噬细胞源性泡沫细胞三磷酸腺苷结合盒转运体A1(ABCA1)和三磷酸腺苷结合盒转运体G1(ABCG1)表达和胆固醇流出的影响,并进一步探讨其可能机制。方法: THP-1单核细胞经佛波酯诱导贴壁后,加入oxLDL诱导其转化为泡沫细胞,经各种因素处理后,用实时荧光定量PCR和Western印迹分别检测基因和蛋白质的表达,运用液体闪烁计数法检测细胞内胆固醇流出,高效液相色谱法分析细胞内总胆固醇、游离胆固醇和胆固醇酯的含量。结果:实验结果表明,IL-6能够明显降低THP-1巨噬细胞源性泡沫细胞ABCA1和ABCG1的表达,抑制细胞内胆固醇的流出。IL-6也能够下调肝X受体α(LXRα)的表达,抑制LXR特异性激动剂T0901317对ABCA1和ABCG1的表达。相反, LXRα-siRNA能逆转IL-6下调ABCA1和ABCG1的作用。同时,IL-6呈剂量和时间依赖性诱导JAK1/STAT3的活化,JAK1抑制剂piceastannol能够抑制IL-6的活化。此外,STAT3小分子干扰RNA和piceastannol能够逆转IL - 6对LXRα、ABCA1和ABCG1的抑制作用。结论:IL-6能抑制THP-1巨噬细胞源性泡沫细胞ABCA1和ABCG1表达及胆固醇流出。这可能是IL-6通过活化JAK1-STAT3信号途径下调LXRα水平,从而降低细胞内ABCA1和ABCG1表达及细胞内胆固醇的流出。
[Abstract]:Aim: to investigate the effects of interleukin-6 (IL-6) on the expression and cholesterol efflux of adenosine triphosphate binding box transporter A1 (ABCA1) and adenosine triphosphate binding box transporter G1 (ABCG1) in THP-1 macrophage derived foam cells. Methods: THP-1 monocytes were induced by phorbol ester and then transformed into foam cells by adding oxLDL. The expression of genes and proteins were detected by real-time fluorescence quantitative PCR and Western blotting. Cholesterol efflux was detected by liquid scintillation counting and the contents of total cholesterol, free cholesterol and cholesterol ester in cells were analyzed by high performance liquid chromatography (HPLC). Results: the results showed that IL-6 could significantly decrease the expression of ABCA1 and ABCG1 in THP-1 macrophage derived foam cells, and inhibit cholesterol efflux. IL-6 could also down-regulate the expression of LXR 伪 in liver. The expression of ABCA1 and ABCG1 was inhibited by LXR specific agonist T0901317. On the contrary, LXR 伪-siRNA reversed the down-regulation of ABCA1 and ABCG1 by IL-6. At the same time, IL-6 induced the activation of JAK1/STAT3 in a dose-and time-dependent manner. JAK1 inhibitor piceastannol could inhibit the activation of IL-6. In addition, the interference of STAT3 with RNA and piceastannol could reverse the inhibitory effect of IL 6 on LXR 伪 -ABCA1 and ABCG1. Conclusion: IL-6 can inhibit the expression of ABCA1 and ABCG1 and cholesterol efflux in THP-1 macrophage derived foam cells. This may be that IL-6 down-regulates the level of LXR 伪 by activating the JAK1-STAT3 signaling pathway, thereby reducing the expression of ABCA1 and ABCG1 and the intracellular cholesterol efflux.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R363

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