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

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.