A molecular pharmacological therapy for asthma based on phenotype changing in the structural cells in airways
| Project/Area Number |
22590846
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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 |
Respiratory organ internal medicine
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| Research Institution | Kinki University |
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Principal Investigator |
KUME Hiroaki 近畿大学, 医学部, 准教授 (50303631)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 気道平滑筋細胞 / 肺血管内皮細胞 / 好酸球 / 気道過敏性亢進 / β_2 アドレナリン受容体 / 気管支喘息 / 低分子量G蛋白 / Rho-kinase / 細胞骨格 / リモデリング / Ca2+動態 / 過剰進展刺激 / フェノタイプ / 気道平滑筋 / 細胞遊走 / サイトカイン / サリドマイド / S1P |
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| Research Abstract |
Sphinosine-1-phosphate (S1P) is released from mast cells by the inflammatory reaction in asthma. The inhibitory effects of β_2-adrenergic receptor agonists were markedly attenuated after exposure of airway smooth muscle to S1P. The expression of adhesion molecules (VCAM-1, ICAM-1) were enhanced after exposure of human pulmonary microvascular endothelial cells to S1P. Adherence of eosinophil to the endothelial cells was also increased under this experimental condition. When an antigen was administrated to sensitized mice, eosinophils and inflammatory cytokines were significantly elevated around airways. Moreover, respiratory resistance in response to methacholine was markedly augmented. All of the phenomena were suppressed by Rho-kinase inhibitors. Hence, RhoA/Rho-kinase pathways may be contributed to the pathophysiology of asthma (β_2-adrenerigic desensitization, eosinophil inflammation, airway hyperresponsiveness etc) implicated in phonotype changes of the structural cells the airways. Rho-kinase may be target protein for asthma therapy.
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Report
(4 results)
Research Products
(48 results)
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[Journal Article] Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma2012
Author(s)
Kotani H, Kishi R, Mouri A, Sashio T, Shindo J, Shiraki A, Hiramatsu T, Iwata S, Taniguchi H, Nishiyama O, Iwata M, Suzuki R, Gonda H, Niwa T, Kondo M, Hasegawa Y, Kume H, Noda Y
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Journal Title
J Clin Pharm Ther
Volume: 371
Pages: 112-6
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Peer Reviewed
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[Journal Article] インダカテロール(新規超長時間作用性β_2 刺激薬)の薬理学的特性とそれに基づく臨床的有用性2011
Author(s)
久米裕昭, 忌部周, 塚本啓造, 沖本奈美, 深 井有美, 山藤啓史, 牧野靖, 西山理, 岩永 賢司, 東本有司, 中島宏和, 東田有智
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Journal Title
アレルギー・免疫
Volume: 18
Pages: 1858-1868
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Peer Reviewed
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[Presentation] Inhibitory effects of Indacaterol on muscarinic activation- and oxidative stress-induced contraction in airway smooth muscle2012
Author(s)
Kume H, Imbe S, Nishiyama O, Sano H, Yamagata T, Iwanaga T, Higashimoto Y, Nakajima H, Tohda Y
Organizer
ATS 2012 International Conference
Place of Presentation
San Francisco, California, U.S.A(Poster Discussion Session)
Year and Date
2012-05-20
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[Book] 喘息治療薬2012
Author(s)
久米裕昭、東田有智
Publisher
カラー版内科学、門脇 孝、永井良三編 西村書店
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