白细胞介素4对THP-1巨噬细胞三磷酸腺苷结合盒转运体A1表达和胆固醇流出的影响
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国家自然科学基金资助项目(81170278、81370377);湖南省自然科学基金面上项目(2015JJ2131);湖南省卫生厅医药卫生科研计划课题项目(B2014-070)


The Effect of Interleukin-4 on ATP-binding Cassette Transporter A1 Expression and Cholesterol Efflux in THP-1 Macrophage
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    摘要:

    目的 探讨白细胞介素4(IL-4)对人类单核细胞株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)表达及细胞内胆固醇流出的影响及机制。方法 THP-1巨噬细胞源性泡沫细胞加入不同浓度的IL-4,处理不同时间,以及加入肝X受体α(LXRα)激动剂T0901317处理后,采用半定量RT-PCR和Western blot分别检测细胞ABCA1及LXRα mRNA和蛋白质的表达,采用油红O染色观察细胞内脂质蓄积情况,使用液体闪烁计法检测细胞内胆固醇流出,采用高效液相色谱法检测细胞内总胆固醇、游离胆固醇和胆固醇酯的量。结果 IL-4能呈浓度和时间依赖性地降低THP-1巨噬细胞源性泡沫细胞ABCA1表达(P<0.05),并减少细胞内胆固醇流出。加入T0901317后能使IL-4对ABCA1的抑制作用减弱(P<0.05)。结论 IL-4能抑制THP-1巨噬细胞源性泡沫细胞ABCA1的表达及胆固醇的流出。LXRα激活能逆转IL-4对ABCA1的抑制作用。

    Abstract:

    Aim To investigate the effects of IL-4 on ATP-binding cassette transporter A1 (ABCA1) expression and cholesterol efflux in human THP-1 macrophage-derived foam cells. Methods THP-1 macrophage-derived foam cells were treated with different concentrations of IL-4, different time, and liver X receptor α (LXRα) agonist T0901317. Semi quantitative RT-PCR and Western blot were used to detect the expressions of ABCA1, LXRα mRNA and protein respectively. Lipid accumulation in cells was observed by oil red O staining. Intracellular cholesterol efflux was detected by using liquid scintillation counting method. Total cholesterol, free cholesterol and cholesterol ester were determined by high performance liquid chromatography. Results IL-4 significantly decreased the expression of ABCA1 in a concentration- and time-dependent manner, and inhibited cholesterol efflux in the THP-1 macrophage-derived foam cells (P<0.05). T0901317 reversed the effect of IL-4 (P<0.05). Conclusions IL-4 decreases ABCA1 expression and inhibites cholesterol efflux in THP-1 macrophage-derived foam cells. LXRα activation can reverse the inhibitory effect of IL-4 on ABCA1.

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谈春芝,谭玉林,姚 峰,谢 魏,张 敏,李 靓,兰 刚,吴 洁,唐朝克.白细胞介素4对THP-1巨噬细胞三磷酸腺苷结合盒转运体A1表达和胆固醇流出的影响[J].中国动脉硬化杂志,2015,23(12):1203~1209.

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  • 收稿日期:2015-07-10
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  • 在线发布日期: 2015-12-26