王婷, 周红, 解鸿翔, 夏龙飞, 穆原. 氟伐他汀抑制抗β2GPI/β2GPI复合物诱导的THP-1细胞活化J. 药学学报, 2013,48(10): 1550-1556.
引用本文: 王婷, 周红, 解鸿翔, 夏龙飞, 穆原. 氟伐他汀抑制抗β2GPI/β2GPI复合物诱导的THP-1细胞活化J. 药学学报, 2013,48(10): 1550-1556.
WANG Ting, ZHOU Hong, XIE Hong-xiang, XIA Long-fei, MU Yuan. Inhibitory effects of fluvastatin on activation of THP-1 cells induced by anti-β2GPI/β2GPI complexJ. Acta Pharmaceutica Sinica, 2013,48(10): 1550-1556.
Citation: WANG Ting, ZHOU Hong, XIE Hong-xiang, XIA Long-fei, MU Yuan. Inhibitory effects of fluvastatin on activation of THP-1 cells induced by anti-β2GPI/β2GPI complexJ. Acta Pharmaceutica Sinica, 2013,48(10): 1550-1556.

氟伐他汀抑制抗β2GPI/β2GPI复合物诱导的THP-1细胞活化

Inhibitory effects of fluvastatin on activation of THP-1 cells induced by anti-β2GPI/β2GPI complex

  • 摘要: 为了探讨氟伐他汀对抗β2GPI/β2GPI复合物诱导THP-1细胞活化的干预作用及机制, 采用脂多糖 (LPS, 500 μgSL-1)、抗β2GPI/β2GPI复合物 (100 mgSL-1) 等活化单核细胞株THP-1并用氟伐他汀 (0、1、5、10及50 mgSL-1) 对细胞进行预处理。采用实时定量PCR (RT-qPCR) 检测细胞组织因子 (TF) 及肿瘤坏死因子-α (TNF-α) mRNA表达, 发色底物法检测TF活性, ELISA方法测定TNF-α蛋白的表达, 蛋白印迹检测细胞NF-κB抑制蛋白 (IκB-α) 和磷酸化NF-κB p65的蛋白水平变化。结果显示, 抗β2GPI/β2GPI复合物 (100 mgSL-1) 能诱导THP-1 细胞活化以及TF和TNF-α表达上调。氟伐他汀 (50 mgSL-1) 能抑制复合物诱导的THP-1细胞TF (mRNA和活性) 及TNF-α (mRNA和蛋白) 的表达 (P < 0.05), 上调IκB-α表达及抑制NF-κB p65磷酸化。结果表明, 氟伐他汀通过干预信号分子IκB-α和磷酸化NF-κB p65的表达, 抑制抗β2GPI/β2GPI复合物诱导的细胞TF及TNF-α的表达, 抑制THP-1细胞活化。

     

    Abstract: This study is to explore the interventional effects of fluvastatin on anti-β2GPI/β2GPI-induced activation in THP-1 mononuclear cells. In vitro, human mononuclear cells THP-1 were treated with fluvastatin, LPS and anti-β2GPI/β2GPI, then the TF expression on THP-1 cells was detected by real-time quantitative PCR (RT-qPCR) or TF activity was detected by kit. TNF-α mRNA and its protein expression were investigated by RT-PCR and ELISA kit. The expression of phospho-NF-κB p65 and inhibitory protein of NF-κB (IκB-α) were measured by Western blotting. The results suggested that the expression of TF and TNF-α on THP-1 cells was significantly up-regulated with treatment of anti-β2GPI/β2GPI complex (100 mgSL-1), compared with that of untreated cells (P < 0.05). Fluvastatin (50 mgSL-1) could decrease TF (mRNA and activity) expression and the level of TNF-α (mRNA and protein) in THP-1 cells with anti-β2GPI/β2GPI complex. The expression of TF and TNF-α was shown in a concentration-dependent manner. Moreover, anti-β2GPI/β2GPI complex could down-regulate IκB-α levels and increase the levels of phospho-NF-κB p65. And these effects of anti-β2GPI/β2GPI complex could be blocked by fluvastatin. In conclusion, fluvastatin may interfere the expression and regulation of NF-κB signal transduction pathway, thereby inhibit the effects of anti-β2GPI/β2GPI on activation of THP-1 cells, by decreasing the expression of TF and TNF-α.

     

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