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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  • TAN Chun-Zhi,TAN Yu-Lin,YAO Feng,XIE Wei,ZHANG Min,LI Jing,LAN Gang,WU Jie,and TANG Chao-Ke

    TAN Chun-Zhi,TAN Yu-Lin,YAO Feng,XIE Wei,ZHANG Min,LI Jing,LAN Gang,WU Jie,and TANG Chao-Ke

    (1.Institute of Cardiovascular Diseases, Key Laboratory for Arteriosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study,University of South China, Hengyang, Hunan 421001, China 2.Key Subject of Immunology, Institute of Pathology, Department of Pathophysiology, Xiangnan University, Chenzhou, Hunan 423000, China 3.Department of Cardiology, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China)
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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
  • 在线发布日期: 2015-12-26