title: Both NF-κB and c-Jun/AP-1 involved in anti-β2GPI/β2GPI-induced tissue factor expression in monocytes.
abstract: 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 (10μg/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.
authors: Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, PR China.
authors: Longfei
authors: L
authors: Xia
authors: Hong
authors: H
authors: Zhou
authors: Lichao
authors: L
authors: Hu
authors: Hongxiang
authors: H
authors: Xie
authors: Ting
authors: T
authors: Wang
authors: Ya
authors: Y
authors: Xu
authors: Jingjing
authors: J
authors: Liu
authors: Xiaolei
authors: X
authors: Zhang
authors: Jinchuan
authors: J
authors: Yan
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D000936:Antigen-Antibody Complex / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation; D053482:beta 2-Glycoprotein I / Q000276:immunology / Q000378:metabolism*
chemical_list: D017152:Antibodies, Antiphospholipid; D000936:Antigen-Antibody Complex; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D016755:Proto-Oncogene Proteins c-jun; C498143:RELA protein, human; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D053482:beta 2-Glycoprotein I; D013925:Thromboplastin