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 (I
κB-
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 I
κB-
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.