| Project/Area Number |
18K08298
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
HIDE Michihiro 広島大学, 医系科学研究科(医), 教授 (50284188)
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| Co-Investigator(Kenkyū-buntansha) |
高萩 俊輔 広島大学, 病院(医), 講師 (40448246)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 蕁麻疹 / 血管内皮細胞 / ヒスタミン / 血液凝固 / 血管透過性 / 数理モデル / 血液凝固因子 / 補体 |
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| Outline of Final Research Achievements |
To elucidate the pathogenesis of urticaria, we developed vascular permeability assessment system with electric impedance sensor and cultured vascular endothelial cell sheet. Using this system, we identified agonists on the innate immune system and cytokines that synergistically increase vascular permeability with histamine. We have demonstrated that histamine increase vascular permeability not only by directly acting on vasculatures, but also by inducing mast cell degranulation via blood coagulation- and complement-system. Moreover, we developed an in vitro model of urticaria which consists of cultured vascular endothelial cell sheet, basophils and monocytes in the presence of human plasma. By this system, we demonstrated that monocytes may trigger the blood coagulation system by expressing tissue factor on their surface in histamine-independent manner. Finally, we succeeded in developing urticaria by a mathematical formula in silico.
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| Academic Significance and Societal Importance of the Research Achievements |
蕁麻疹はヒト、ウマ、チンパンジーなどのごく限られた哺乳動物に見られる疾患で、その約3/4は、明らかな原因、誘因なく症状出現を繰り返す特発性の蕁麻疹である。その約半数は抗ヒスタミン薬が奏効するが、半数近くは効果不十分で、たとえ効果があった場合でも薬剤治療を中止すると再び症状が現れるためにその社会的負担は極めて大きい。本研究は、蕁麻疹の病態解明のためのin vitroモデルを構築し、その病態にこれまでほとんど注目されてこなかった血液凝固と補体の経路が重要であることを証明し、抗ヒスタミン薬が無効な症例がある理由、またそれらの症例を含む蕁麻疹に対する新たな治療標的を示した。
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