Anti-beta(2)GPI/beta(2)GPI stimulates activation of THP-1 cells through TLR4/MD-2/MyD88 and NF-kappa B signaling pathways

作者：Zhou, Hong^*; Sheng, Liangju; Wang, Haibo; Xie, Hongxiang; Mu, Yuan; Wang, Ting; Yan, Jinchuan

来源：Thrombosis Research, 2013, 132(6): 742-749.

DOI：10.1016/j.thromres.2013.09.039

• Anti-beta(2)-glycoprotein I antibodies
• beta(2)-glycoprotein I
• THP-1 cells
• proinflammatory molecules
• TLR4/MD-2/MyD88
• NF-kappa B

Our previous study demonstrated that Toll-like receptor 4 (TLR4) could act as a co-receptor with annexin A2 (ANX2) mediating anti-beta(2)-glycoprotein I/beta(2)-glycoprotein I (anti-beta(2)GPI/beta(2)GPI) -induced tissue factor (TF) expression in human acute monocytic leukaemia cell line THP-1. In the current study, we further explored the roles of TLR4 and its adaptors, MD-2 and MyD88, as well as nuclear factor kappa B (NF-kappa B), in anti-beta(2)GPI/beta(2)GPI-induced the activation of THP-1 cells, especially on the expression of some proinflammatory molecules. The results showed that treatment of THP-1 cells with anti-beta(2)GPI (10 mu g/ml)/beta(2)GPI (100 mu g/ml) complex could increase IL-6 (interleukin-6), IL-8 (interleukin-8) as well as TNF-alpha (tumor necrosis factor alpha) expression (both mRNA and protein levels). These effects could be blocked by addition of TAK-242 (5 mu M), a blocker of signaling transduction mediated by the intracellular domain of TLR4, and also by NF-kappa B inhibitor PDTC (20 mu M). Overall, our results indicate that anti-beta(2)GPI/beta 2GPI complex induced IL-6, IL-8 and TNF-alpha expression involving TLR4/MD-2/MyD88 and NF-kappa B signaling pathways and this might be associated with pathological mechanisms of antiphospholipid syndrome (APS).

• 出版日期2013-12
• 单位江苏大学