Study of urticaria with cultured endothelial cell sheet model and blood coagulation factors of blood coagulation factors
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 |
Section | 一般 |
Review Section |
Basic Section 53050:Dermatology-related
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Research Institution | Hiroshima University |
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 |
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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Report
(4 results)
Research Products
(104 results)
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[Journal Article] Definition, aims, and implementation of GA2 LEN/HAEi Angioedema Centers of Reference and Excellence.2020
Author(s)
Maurer M, Aberer W, Agondi R, Al-Ahmad M, Al-Nesf MA, Ansotegui I, Arnaout R, Arruda LK, Asero R, Aygoren-Pursu E (49番目にFukunaga A, 59番目にHide M)et al
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Journal Title
Allergy
Volume: 75
Issue: 8
Pages: 2115-23
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Japanese guidelines for atopic dermatitis 20202020
Author(s)
Katoh N, Ohya Y, Ikeda M, Ebihara T, Katayama I, Saeki H, Shimojo N, Tanaka A, Nakahara T, Nagao M, Hide M, Fujita Y, Fujisawa T, Futamura M, Masuda K, Murota H, Yamamoto-Hanada K
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Journal Title
Allergology International
Volume: 69
Issue: 3
Pages: 356-369
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access
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[Journal Article] Changes in the characteristics of patients with latex allergy from 1999 to 20142020
Author(s)
Kawai M, Kondo Y, Nakajima Y, TsugeI, Yoshikawa T, Yagam A, Aihara M, Ikezawa Z, Ohya Y, Kitabayashi T, Saito H, Shibata R, Naito T, Harada S, Hide M, Matsunaga K, Miyasaka K, Akasawa A.
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Journal Title
Fujita Medical Journal
Volume: 6
Issue: 3
Pages: 67-72
DOI
NAID
ISSN
2189-7247, 2189-7255
Related Report
Peer Reviewed
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[Journal Article] Histamine- or vascular endothelial growth factor-induced tissue factor expression and gap formation between vascular endothelial cells are synergistically enhanced by lipopolysaccharide, tumor necrosis factor-alpha, interleukin (IL)-33 or IL-1b.2020
Author(s)
Kamegashira A, Yanase Y, Takahagi S, Saito R, Uchida K, Kawaguchi T, Ishii K, Tanaka A, Ozawa K, Hide M
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Journal Title
J Dermatol
Volume: 47
Issue: 11
Pages: 1293-1300
DOI
Related Report
Peer Reviewed
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[Journal Article] Long-term dynamics of omega-5 gliadin-specific IgE levels in patients with adult-onset wheat allergy2020
Author(s)
Hamada Y, Chinuki Y, Fukutomi Y, Nakatani E, Yagami A, Matsunaga K, Oda Y, Fukunaga A, Adachi A, Hiragun M, Hide M, Morita E
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Journal Title
J Allergy Clin Immunol Pract.
Volume: 8
Issue: 3
Pages: 1149-1151
DOI
Related Report
Peer Reviewed
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[Journal Article] HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy2019
Author(s)
Noguchi E, Akiyama M, Yagami A, Hirota T, Okada Y, Kato Z, Kishikawa R, Fukutomi Y, Hide M, Morita E, Aihara M, Hiragun M, Chinuki Y, Okabe T, Ito A, Adachi A, Fukunaga A, Kubota Y, Aoki T, Aoki Y, Nishioka K, Adachi T, et al.
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Journal Title
J Aller Clin Immunol
Volume: 144
Issue: 5
Pages: 1354-1363
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Efficacy and safety of omalizumab for the treatment of refractory chronic spontaneous urticaria in Japanese patients: Subgroup analysis of the phase 3 POLARIS study2018
Author(s)
Hide M, Igarashi A, Yagami A, Chinuki Y, Inomata N, Fukunaga A, Kaiser G, Wang J, Matsushima S, Greenberg S, Khalil S.
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Journal Title
Allergology International
Volume: 67
Issue: 2
Pages: 243-252
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The EAACI/GA(2)LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria2018
Author(s)
Zuberbier T, Aberer W, Asero R, Abdul Latiff AH, Baker D, Ballmer-Weber B, Bernstein JA, Bindslev-Jensen C, Brzoza Z, Buense Bedrikow R, Canonica GW, Church MK, Craig T, Danilycheva IV, Dressler C, Ensina LF, Gimenez-Arnau A, Godse K, Goncalo M, Grattan C, Hebert J, Hide M, et al.
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Journal Title
Allergy
Volume: 73
Issue: 7
Pages: 1393-1414
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update2018
Author(s)
Maurer M, Magerl M, Ansotegui I, Aygoren-Purun E, Betschel S, Bork K, Bowen T, Balle Boysen H, Farkas H, Grumach AS, Hide M, et al.
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Journal Title
Allergy
Volume: 73
Issue: 8
Pages: 1575-1596
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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