title: The Effects of NF-κB and c-Jun/AP-1 on the Expression of Prothrombotic and Proinflammatory Molecules Induced by Anti-β2GPI in Mouse.
abstract: Our previous data demonstrated that nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) are involved in the process of anti-β2GPI/β2GPI-induced tissue factor (TF) expression in monocytes. However, the role of NF-κB and AP-1 in pathogenic mechanisms of antiphospholipid syndrome (APS) in vivo has been rarely studied. This study aimed to investigate whether NF-κB and c-Jun/AP-1 are involved in anti-β2GPI-induced expression of prothrombotic and proinflammatory molecules in mouse. IgG-APS or anti-β2GPI antibodies were injected into BALB/c mice in the presence or absence of PDTC (a specific inhibitor of NF-κB) and Curcumin (a potent inhibitor of AP-1) treatment. Our data showed that both IgG-APS and anti-β2GPI could induce the activation of NF-κB and c-Jun/AP-1 in mouse peritoneal macrophages. The anti-β2GPI-induced TF activity in homogenates of carotid arteries and peritoneal macrophages from mice could significantly decrease after PDTC and/or Curcumin treatment, in which PDTC showed the strongest inhibitory effect, but combination of two inhibitors had no synergistic effect. Furthermore, anti-β2GPI-induced expression of TF, VCAM-1, ICAM-1 and E-selectin in the aorta and expression of TF, IL-1β, IL-6 and TNF-α in peritoneal macrophages of mice were also significantly attenuated by PDTC and/or Curcumin treatment. These results indicate that both NF-κB and c-Jun/AP-1 are involved in regulating anti-β2GPI-induced expression of prothrombotic and proinflammatory molecules in vivo. Inhibition of NF-κB and c-Jun/AP-1 pathways may be beneficial for the prevention and treatment of thrombosis and inflammation in patients with APS.
authors.affiliation: Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Xia
authors.affiliation: Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Yinjing
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China.|Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D016736:Antiphospholipid Syndrome / Q000276:immunology; D003474:Curcumin / Q000494:pharmacology; D019040:E-Selectin / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D000906:Antibodies; D019040:E-Selectin; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D013859:Thiocarbamates; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D053482:beta 2-Glycoprotein I; D018799:Intercellular Adhesion Molecule-1; C066229:prolinedithiocarbamate; D013925:Thromboplastin; D011392:Proline; D003474:Curcumin
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