title: Anti-β2GPI/β2GPI stimulates activation of THP-1 cells through TLR4/MD-2/MyD88 and NF-κB signaling pathways.
abstract: Our previous study demonstrated that Toll-like receptor 4 (TLR4) could act as a co-receptor with annexin A2 (ANX2) mediating anti-β2-glycoprotein I/β2- glycoprotein I (anti-β2GPI/β2GPI) -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-κB), in anti-β2GPI/β2GPI-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-β2GPI (10μg/ml)/β2GPI (100μg/ml) complex could increase IL-6 (interleukin-6), IL-8 (interleukin-8) as well as TNF-α (tumor necrosis factor alpha) expression (both mRNA and protein levels). These effects could be blocked by addition of TAK-242 (5μM), a blocker of signaling transduction mediated by the intracellular domain of TLR4, and also by NF-κB inhibitor PDTC (20μM). Overall, our results indicate that anti-β2GPI/β2GPI complex induced IL-6, IL-8 and TNF-α expression involving TLR4/MD-2/MyD88 and NF-κB signaling pathways and this might be associated with pathological mechanisms of antiphospholipid syndrome (APS).
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: hongzhou@ujs.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Liangju
authors.initials: L
authors.lastname: Sheng
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Xie
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mu
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
mesh_terms: D000936:Antigen-Antibody Complex / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D051218:Lymphocyte Antigen 96 / Q000276:immunology / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000276:immunology / Q000378:metabolism*
chemical_list: D000936:Antigen-Antibody Complex; D015850:Interleukin-6; D016209:Interleukin-8; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D053482:beta 2-Glycoprotein I
keywords: Anti-β(2)-glycoprotein I antibodies; NF-κB; THP-1 cells; TLR4/MD-2/MyD88; proinflammatory molecules; β(2)-glycoprotein I