Studies on thrombophilic diathesis and development of a novel molecular-targeting therapy in antiphospholipid syndrome
| Project/Area Number |
20591165
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KUBOTA Tetsuo Tokyo Medical and Dental University, 大学院・保健衛生学研究科, 准教授 (90205138)
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| Co-Investigator(Kenkyū-buntansha) |
UMEZAWA Kazuo 慶応義塾大学, 理工学部, 教授 (70114402)
鈴木 英紀 (財)東京都医学研究機構, 電子顕微鏡室, 主任研究員 (30158977)
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| Co-Investigator(Renkei-kenkyūsha) |
SUZUKI Hidenori (財)東京都医学研究機構, 電子顕微鏡室, 主任研究員 (30158977)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 抗リン脂質抗体症候群 / 抗β2-グリコプロテインI抗体 / 動物モデル / NF-kappaB / 抗β2グリコプロテインI抗体 / シグナル伝達阻害薬 / 血小板機能 / ケモカイン |
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| Research Abstract |
IgG fraction of patients with systemic lupus erythematosus (SLE) who had anti-β2-glycoprotein I (β2-GPI) antibodies induced expression of inflammatory cytokines such as IL-1β and TNFα, and tissue factor with procoagulant activity on peripheral blood mononuclear cells from healthy volunteers. On vascular endothelial cells, IL-1β and TNFα induced CX3CL1 which in turn increased platelet adhesive activity to collagen, and CCL5 which induced platelet aggregation. Expression of these cytokines, chemokines and tissue factor was all suppressed by a novel NF-κB inhibitor DHMEQ. In addition, a mouse model of antiphospholipid syndrome (APS) was established in which prothrombotic status was induced by injection of anti-β2-GPI antibodies form patients or newly made monoclonal anti-β2-GPI antibody. The monoclonal antibody showed cross-reactivity with double-stranded(ds)DNA, suggesting the common mechanism playing a role in pathogenesis of SLE and APS.
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Report
(4 results)
Research Products
(17 results)
