南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (09): 1269-1272.

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巨噬细胞中ABCA1对炎症因子的调节及其意义

郭志刚； 吴平生； 李建华； 赖文岩；   

  1. 南方医科大学南方医院心内科； 南方医科大学南方医院心内科 广东广州510515； 广东广州510515；
  • 出版日期:2006-09-20 发布日期:2006-09-20
  • 基金资助:
    国家自然科学基金(30171028);广东省自然科学基金(010616)~~

Modulation of inflammatory cytokines by ATP-binding cassette A1 in THP-1 macrophages

GUO Zhi-gang, WU Ping-sheng, LI Jian-hua, LAI Wen-yan Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China   

  1. 南方医科大学南方医院心内科； 南方医科大学南方医院心内科 广东广州510515； 广东广州510515；
  • Online:2006-09-20 Published:2006-09-20

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摘要： 目的研究在8-溴-环磷酸腺苷(8-Br-cAMP)刺激下,巨噬细胞中三磷酸腺苷结合盒转运子(ABCA1)对细胞间黏附分子-1(ICAM-1)、单核细胞化学趋向蛋白-1(MCP-1)及白介素-1β(IL-1β)的调节作用,在细胞水平证实ABCA1在动脉粥样硬化发生中的作用机制。方法用氟波酯(PMA)刺激THP-1细胞使之转变为巨噬细胞,8-Br-cAMP(0.5mmol/L)刺激3、6、12、24h后,以荧光定量RT-PCR和Western蛋白印迹法及ELISA法检测ABCA1、ICAM-1、MCP-1及IL-1βmRNA和蛋白质表达量;用反义寡核苷酸(100nmol/L)抑制ABCA1的表达,观察Ox-LDL刺激下上述指标的改变。结果予8-Br-cAMP刺激6、12h后,巨噬细胞ABCA1、ICAM-1、MCP-1mRNA和蛋白质水平及IL-1β蛋白质水平均增高;反义寡核苷酸转染巨噬细胞,8-Br-cAMP刺激后3、6h,ABCA1、ICAM-1、MCP-1mRNA的表达降低,刺激后12、24h,ABCA1、ICAM-1、MCP-1及IL-1β蛋白质的表达水平降低。结论在8-Br-cAMP刺激下,巨噬细胞ABCA1可增加炎症因子表达,参与动脉粥样硬化的发生。

Abstract: Objective To observe the effects of ATP-binding cassette A1 (ABCA1) on intercellular cell adhesion molecule type 1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and interleukin-1β (IL-1β) in THP-1 macrophages stimulated with 8-Br-cAMP to identify a possible new mechanism that ABCA1 contributes to atherosclerogenesis (AS). Methods Monocytic THP-1 cells were cultured in the presence of 100 nmol/L phorbol myristate acetate (PMA) for 72 h to transform the cells into THP-1 macrophages. After the macrophages were stimulated with 8-Br-cAMP (final concentration 0.5 mmol/L) for 3, 6, 12 and 24 h respectively, the amounts of ABCA1, ICAM-1 and MCP-1 mRNA were examined by real-time fluorescent quantitative RT-PCR, and the protein amounts of ABCA1, ICAM-1, MCP-1 and IL-1β were determined by Western blotting and enzyme-linked immunosorbent assay (ELISA). Phosphorothioate antisense oligonucleotides of ABCA1 were add into the culture media at a final concentration of 100 nmol/L and the experiments were repeated. Results ABCA1, ICAM-1 and MCP-1 mRNA and protein and IL-1β protein were increased in the macrophages after stimulation with 8-Br-cAMP for 6 and 12 h. The mRNA expressions of ABCA1, ICAM-1 and MCP-1 were decreased significantly at 3 and 6 h (P<0.01), and the protein expressions of ABCA1, ICAM-1, MCP-1 and IL-1β declined significantly at 12 and 24 h (P<0.01) after transfection of the macrophages with antisense oligonucleotides of ABCA1. Conclusion ABCA1 can increase the expressions of the inflammatory cytokines in THP-1 macrophages stimulated by 8-Br-cAMP and plays a role in the pathogenesis of AS. 

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