氟伐他汀对抗β2糖蛋白I/β2糖蛋白I复合物诱导的THP-1细胞活化的抑制作用

[Inhibitory effects of fluvastatin on activation of THP-1 cells induced by anti-beta2GPI/beta2GPI complex].

作者信息

Wang Ting, Zhou Hong, Xie Hong-Xiang, Xia Long-Fei, Mu Yuan

机构信息

School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China.

出版信息

Yao Xue Xue Bao. 2013 Oct;48(10):1550-6.

PMID:24417081

Abstract

This study is to explore the interventional effects of fluvastatin on anti-beta2GPI/beta2GPI-induced activation in THP-1 mononuclear cells. In vitro, human mononuclear cells THP-1 were treated with fluvastatin, LPS and anti-beta2GPI/beta2GPI, 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-alpha mRNA and its protein expression were investigated by RT-PCR and ELISA kit. The expression of phospho-NF-kappaB p65 and inhibitory protein of NF-kappaB (IkappaB-alpha) were measured by Western blotting. The results suggested that the expression of TF and TNF-alpha on THP-1 cells was significantly up-regulated with treatment of anti-beta2GPI/beta2GPI complex (100 mg x L(-1)), compared with that of untreated cells (P < 0.05). Fluvastatin (50 mg x L(-1)) could decrease TF (mRNA and activity) expression and the level of TNF-alpha (mRNA and protein) in THP-1 cells with anti-beta2GPI/beta2GPI complex. The expression of TF and TNF-alpha was shown in a concentration-dependent manner. Moreover, anti-beta2GPI/beta2GPI complex could downregulate IkappaB-alpha levels and increase the levels of phospho-NF-kappaB p65. And these effects of anti-beta2GPI/beta2GPI complex could be blocked by fluvastatin. In conclusion, fluvastatin may interfere the expression and regulation of NF-kappaB signal transduction pathway, thereby inhibit the effects of anti-beta2GPI/beta2GPI on activation of THP-1 cells, by decreasing the expression of TF and TNF-alpha.

摘要

本研究旨在探讨氟伐他汀对THP - 1单核细胞中抗β2GPI/β2GPI诱导激活的干预作用。在体外，将人单核细胞THP - 1用氟伐他汀、脂多糖（LPS）和抗β2GPI/β2GPI处理，然后通过实时定量聚合酶链反应（RT - qPCR）检测THP - 1细胞上组织因子（TF）的表达，或用试剂盒检测TF活性。通过RT - PCR和酶联免疫吸附测定（ELISA）试剂盒研究肿瘤坏死因子α（TNF - α）mRNA及其蛋白表达。通过蛋白质免疫印迹法检测磷酸化核因子κB p65（phospho - NF - κB p65）和核因子κB抑制蛋白（IkappaB - α）的表达。结果表明，与未处理细胞相比，用抗β2GPI/β2GPI复合物（100 mg·L⁻¹）处理后，THP - 1细胞上TF和TNF - α的表达显著上调（P < 0.05）。氟伐他汀（50 mg·L⁻¹）可降低抗β2GPI/β2GPI复合物处理的THP - 1细胞中TF（mRNA和活性）的表达以及TNF - α（mRNA和蛋白）的水平。TF和TNF - α的表达呈浓度依赖性。此外，抗β2GPI/β2GPI复合物可下调IkappaB - α水平并增加磷酸化核因子κB p65的水平。氟伐他汀可阻断抗β2GPI/β2GPI复合物的这些作用。总之，氟伐他汀可能通过干扰核因子κB信号转导通路的表达和调节，从而通过降低TF和TNF - α的表达来抑制抗β2GPI/β2GPI对THP - 1细胞激活的作用。