Both NF-κB and c-Jun/AP-1 involved in anti-β₂GPI/β₂GPI-induced tissue factor expression in monocytes

 

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Summary

Our previous data has demonstrated that Toll-like receptor 4 (TLR4) and its signalling pathway can contribute to anti-β₂-glycoprotein I/β₂-glycoprotein I (anti-β₂GPI/β₂GPI) -induced tissue factor (TF) expression in human blood monocytes and acute monocytic leukaemia cell line THP-1. However, its downstream nuclear transcription factors have not been well explored. In the current study, we further investigated whether nuclear factor kappa B (NF-κB) and activator protein (AP-1) were activated and their roles in anti-β₂GPI/β₂GPI complex stimulating TF expression. The results showed that treatment of the cells with anti-β₂GPI (10 µg/ml)/β₂GPI (100 mg/ml) complex could markedly increase the levels of phosphorylated NF-κB (p-NF-κB p65) and c-Jun/AP-1 (p-c-Jun), as well as TF expression. Both NF-κB inhibitor PDTC (20 µM) and AP-1 inhibitor curcumin (25 mM) could attenuate TF expression induced by anti-β₂GPI/β₂GPI or APS-IgG/β₂GPI complex. Combination of any two inhibitors of MAPKs (SB203580/U0126 or SB203580/SP600125 or U0126/SP600125) could decrease activation of NF-κB. SB203580/SP600125 or U0126/SP600125, but not SB203580/U0126, could reduce the phosphorylation of c-Jun/AP-1. Neither NF-κB nor c-Jun/AP-1 activation caused by anti-β₂GPI/β₂GPI complex could be affected by TLR4 inhibitor TAK-242. In conclusion, our results indicate that both NF-κB and c-Jun/AP-1 can be activated and play important roles in the process of anti-β₂GPI/β₂GPI-induced TF expression in monocytes, thereby contributing to the pathological processes of antiphospholipid syndrome.

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