title: Anti-β(2)GPI/β(2)GPI induced TF and TNF-α expression in monocytes involving both TLR4/MyD88 and TLR4/TRIF 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-β(2)GPI/β(2)GPI)-induced tissue factor (TF) expression in human acute monocytic leukemia cell line THP-1. In the current study, we further explored the roles of TLR4 and its adaptors, MyD88 and TRIF, in anti-β(2)GPI/β(2)GPI-induced the activation of human blood monocytes and THP-1 cells and the relationship among TLR4, β(2)GPI and ANX2 in this process. The results showed that treatment of monocytes or THP-1 cells with anti-β(2)GPI/β(2)GPI complex could increase TF, MyD88, TRIF as well as TNF-α (tumor necrosis factor alpha) expression. These effects were blocked by addition of TAK-242, a blocker of signaling transduction mediated by the intracellular domain of TLR4. Moreover, TLR4/β(2)GPI/ANX2 complex could be detected in THP-1 cell lysates. Overall, our results indicate that anti-β(2)GPI/β(2)GPI complex induced TF and TNF-α expression involving both TLR4/MyD88 and TLR4/TRIF signaling pathways and TLR4 and its adaptors might be molecular targets for therapy of antiphospholipid syndrome (APS).
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Xie
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Dongdong
authors.initials: D
authors.lastname: Chen
authors.forename: Longfei
authors.initials: L
authors.lastname: Xia
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D017306:Annexin A2 / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000276:immunology* / Q000378:metabolism
chemical_list: C472822:ANXA2 protein, human; D033942:Adaptor Proteins, Vesicular Transport; D017306:Annexin A2; D000936:Antigen-Antibody Complex; D017931:DNA Primers; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D013449:Sulfonamides; C470409:TICAM1 protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D053482:beta 2-Glycoprotein I; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate; D013925:Thromboplastin