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A molecular pharmacological therapy for asthma based on phenotype changing in the structural cells in airways

Research Project

Project/Area Number 22590846
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKinki University

Principal Investigator

KUME Hiroaki  近畿大学, 医学部, 准教授 (50303631)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
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)
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
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.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (48 results)

All 2012 2011 2010

All Journal Article (17 results) (of which Peer Reviewed: 16 results) Presentation (25 results) (of which Invited: 3 results) Book (6 results)

  • [Journal Article] Role of sphingosine-1-phosphate in r-adrenoceptor desensitization via Ca2+ sensitization in airway smooth muscle2012

    • Author(s)
      Makino Y, Kume H, Oguma T, Sugishita M, Shiraki A, Hasegawa Y, Honjo H, Kamiya K
    • Journal Title

      Allergol Int

      Volume: 61 Pages: 311-22

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Possible Involvement of Sphingosine-1-Phosphate/Gi/RhoA pathways in adherence of eosinophils to pulmonary endothelium.2012

    • Author(s)
      Sashio T, Kume H, Takeda N, Asano T, Tsuji S, Kondo M, Hasegawa Y, Shimokata K
    • Journal Title

      Allergol Int

      Volume: 61 Pages: 283-93

    • NAID

      130004477122

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      J Clin Pharm Ther

      Volume: 371 Pages: 112-6

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of Sphingosine-1-Phosphate in &#946;-adrenoceptor Desensitization via Ca<sup>2+</sup> Sensitization in Airway Smooth Muscle2012

    • Author(s)
      Makino Y
    • Journal Title

      Allergology International

      Volume: 61 Issue: 2 Pages: 311-322

    • DOI

      10.2332/allergolint.11-OA-0350

    • NAID

      130004477126

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible Involvement of Sphingosine-1-Phosphate/G<sub>i</sub>/RhoA Pathways in Adherence of Eosinophils to Pulmonary Endothelium2012

    • Author(s)
      Sashio T
    • Journal Title

      Allergology International

      Volume: 61 Issue: 2 Pages: 283-293

    • DOI

      10.2332/allergolint.10-OA-0299

    • NAID

      130004477122

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of Sphingosine-1-Phosphate in β-adrenoceptor Desensitization via Ca2+ Sensitization in Airway Smooth Muscle2012

    • Author(s)
      Makino Y
    • Journal Title

      Allergol Int

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible Involvement of Sphingosine-1-Phosphate/G(i)/RhoA Pathways in Adherence of Eosinophils to Pulmonary Endothelium2012

    • Author(s)
      Sashio T
    • Journal Title

      Allergol Int

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] COPD 治療におけるβ_2 刺激薬の特性2011

    • Author(s)
      久米裕昭、東田有智
    • Journal Title

      吸入療法

      Volume: 3 Pages: 30-40

    • Related Report
      2012 Final Research Report
  • [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
    • Journal Title

      アレルギー・免疫

      Volume: 18 Pages: 1858-1868

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [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
    • Journal Title

      アレルギー・免疫

      Volume: 18 Pages: 1-858

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thalidomide attenuates airway hyperresponsiveness and eosinophilic inflammation in a murine model of allergic asthma2010

    • Author(s)
      Asano T, Kume H, Taki F, Ito S, Hasegawa Y
    • Journal Title

      Biol Pharm Bull

      Volume: 33 Pages: 1028-32

    • NAID

      130000247974

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Actin cytoskeleton regulates stretch-activated Ca2+ influx in human pulmonary microvascular endothelial cells2010

    • Author(s)
      Ito S, Suki B, Kume H, Numaguchi Y, Ishii M, Iwaki M, Kondo M, Naruse K, Hasegawa Y, Sokabe M
    • Journal Title

      Am J Respir Cell Mol Biol

      Volume: 43 Pages: 26-34

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 慢性閉塞性肺疾患に潜伏する好酸球性気道 炎症に対する制御と吸入ステロイド薬/長時間 作用性 β_2 刺激薬配合剤の有用性―あらたな 臨床病型の可能性2010

    • Author(s)
      久米裕昭、辻 清太、塚本啓造、忌部 周、山 藤啓史、綿谷奈々瀬、宮嶋宏之、西川裕作、 中島宏和、東田有智
    • Journal Title

      アレルギー・免疫

      Volume: 17 Pages: 2056-2065

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 慢性閉塞性肺疾患の肺機能改善における短時間作用性 β_2 刺激薬の有効性―固有活性に基づいた効果の検討2010

    • Author(s)
      久米裕昭、白木 晶、綿谷奈々瀬、西川裕作、川内映理、佐藤隆司、東本有司、宮良高維、中島宏和、東田有智
    • Journal Title

      アレルギー・免疫

      Volume: 17 Pages: 1230-1238

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thalidomide attenuates airway hyperresponsiveness and eosinophilic inflammation in a murine model of allergic asthma.2010

    • Author(s)
      Asano T, et al.
    • Journal Title

      Biol Pharm Bull

      Volume: 33 Pages: 1028-1032

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 慢性閉塞性肺疾患の肺機能改善における短時間作用性β_2刺激薬の有効性-固有活性に基づいた効果の検討2010

    • Author(s)
      久米裕昭, 他
    • Journal Title

      アレルギー・免疫

      Volume: 17 Pages: 1230-1238

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 慢性閉塞性肺疾患に潜伏する好酸球性気道炎症に対する制御と吸入ステロイド薬/長時間作用性β_2刺激薬配合剤の有用性-あらたな臨床病型の可能性2010

    • Author(s)
      久米裕昭, 他
    • Journal Title

      アレルギー・免疫

      Volume: 17 Pages: 2056-2065

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 気道炎症からみた喘息とCOPD の接点喘息とCOPD の接点2012

    • Author(s)
      久米裕昭、東田有智
    • Organizer
      第62回日本アレルギー学会秋季学術大会
    • Place of Presentation
      大阪市(シンポジウム)
    • Year and Date
      2012-11-30
    • Related Report
      2012 Final Research Report
  • [Presentation] Synergistic effects of glycopyronium bromide and indacaterol on muscarinic agonist-induced contraction in airway smooth muscle2012

    • Author(s)
      Kume H, Imbe S, Iwanaga T, Tohda Y
    • Organizer
      ERS Annual Congress-Vienna 2012
    • Place of Presentation
      Austria(Poster Discussion)
    • Year and Date
      2012-09-05
    • Related Report
      2012 Final Research Report
  • [Presentation] あらたな喘息分子薬理療法の可能性-標的分子としてのRhoA/Rho-kinase 系2012

    • Author(s)
      久米裕昭、東田有智
    • Organizer
      第32回六甲カンファレンス
    • Place of Presentation
      京都市
    • Year and Date
      2012-07-29
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [Presentation] Future Risk の予防に求められる LABAの必要性とその特性 Next stage of asthma treatment2012

    • Author(s)
      久米裕昭、東田有智
    • Organizer
      第24回日本アレルギー学会春季臨床大会
    • Place of Presentation
      大阪市(ランチプログラム)
    • Year and Date
      2012-05-13
    • Related Report
      2012 Final Research Report
  • [Presentation] 好酸球性気道炎症に基づく吸入ステロイド薬の有効性 COPD と喘息:治療の接点2012

    • Author(s)
      久米裕昭、東田有智
    • Organizer
      第24回日本アレルギー学会春季臨床大会
    • Place of Presentation
      大阪市(シンポジウム)
    • Year and Date
      2012-05-13
    • Related Report
      2012 Final Research Report
  • [Presentation] Indacaterol(超長時間作用性β_2 アドレナリン受容体刺激薬)の特徴とそれに基づく臨床的有用性2012

    • Author(s)
      久米裕昭、忌部 周、塚本敬造、深井有美、 牧野 靖、佐藤隆司、西山 理、佐野博幸、 岩永賢司、東田有智
    • Organizer
      第52回日本呼吸器学会学術講演会
    • Place of Presentation
      神戸市
    • Year and Date
      2012-04-22
    • Related Report
      2012 Final Research Report
  • [Presentation] 慢性閉塞性肺疾患の新たな表現型-好酸球性気道炎症と気道過敏性からみた病型分類2012

    • Author(s)
      久米裕昭、沖本奈美、深井有美、忌部 周、宮嶋宏之、西山 理、岩永賢司、東本有司、に鹿島宏和、東田有智
    • Organizer
      第52回日本呼吸器学会学術講演会
    • Place of Presentation
      神戸市
    • Year and Date
      2012-04-21
    • Related Report
      2012 Final Research Report
  • [Presentation] Synergistic effects of glycopyronium bromide and indacaterol on muscarinic agonist-induced contraction in airway smooth muscle.2012

    • Author(s)
      Kume H
    • Organizer
      ERS Annual Congress-Vienna 2012
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2012 Annual Research Report
  • [Presentation] Inhibitory effects of Indacaterol on muscarinic activation- and oxidative stress-induced contraction in airway smooth muscle.2012

    • Author(s)
      Kume H
    • Organizer
      ATS 2012 International Conference
    • Place of Presentation
      San Francisco, California, U.S.A.
    • Related Report
      2012 Annual Research Report
  • [Presentation] 気道炎症からみた喘息とCOPDの接点2012

    • Author(s)
      久米裕昭
    • Organizer
      第62回日本アレルギー学会秋季学術大会
    • Place of Presentation
      大阪国際会議場、大阪市
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Future Risk の予防に求められる LABA の必要性とその特性2012

    • Author(s)
      久米裕昭
    • Organizer
      第24回日本アレルギー学会春季臨床大会
    • Place of Presentation
      大阪国際会議場、大阪市
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 好酸球性気道炎症に基づく吸入ステロイド薬の有効性2012

    • Author(s)
      久米裕昭
    • Organizer
      第24回日本アレルギー学会春季臨床大会
    • Place of Presentation
      大阪国際会議場、大阪市
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Indacaterol(超長時間作用性β_2 アドレナリン受容体刺激薬)の薬理学的特性について2011

    • Author(s)
      久米裕昭、塚本敬造、忌部 周、牧野 靖、岩永賢司、中島宏和、東田有智
    • Organizer
      第61回日本アレルギー学会秋季術大会
    • Place of Presentation
      東京
    • Year and Date
      2011-11-10
    • Related Report
      2012 Final Research Report
  • [Presentation] A novel classification and rational use ofβ_2-sdrenerigic agonists based on their intrinsic efficacy2011

    • Author(s)
      Kume H, Sugishita M, Maino Y, Tohda y
    • Organizer
      ATS 2011 International Conference
    • Place of Presentation
      Denver, Colorado, U.S.A.
    • Year and Date
      2011-05-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Novel classification and rational use of β_2-adrenergic receptor agonists based on their intrinsic efficacy2011

    • Author(s)
      Kume H
    • Organizer
      2011 ATS International Conference
    • Place of Presentation
      米国コロラド州デンバー市
    • Year and Date
      2011-05-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] 喘息と末梢気道閉塞呼吸機能検査の未来への第一歩:末梢気道閉塞を問い直す2011

    • Author(s)
      久米裕昭、岩永賢司、東田有智
    • Organizer
      第51回日本呼吸器学会学術講演会
    • Place of Presentation
      東京(シンポジウム)
    • Year and Date
      2011-04-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 吸入ステロイド薬に対する反応 高齢者喘息とCOPD の類似点・相違点2010

    • Author(s)
      久米裕昭、東田有智
    • Organizer
      第60回日本アレルギー学会秋季学実大会高齢者喘息とCOPD の類似点・相違点
    • Place of Presentation
      東京(ワークショップ)
    • Year and Date
      2010-11-27
    • Related Report
      2012 Final Research Report
  • [Presentation] 吸入ステロイド薬に対する反応-高齢者喘息とCOPDの類似点・相違点2010

    • Author(s)
      久米裕昭
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京
    • Year and Date
      2010-11-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] 高齢者喘息 喘息を取り巻く最近の話題2010

    • Author(s)
      久米裕昭、東田有智
    • Organizer
      第60回日本アレルギー学会秋季学実大会
    • Place of Presentation
      東京(イブニングシンポシウム)
    • Year and Date
      2010-11-26
    • Related Report
      2012 Final Research Report
  • [Presentation] 高齢者喘息-喘息を取り巻く最近の話題2010

    • Author(s)
      久米裕昭
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京
    • Year and Date
      2010-11-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 高齢者喘息の問題点~患者に適した治療を求めて~2010

    • Author(s)
      久米裕昭、東田有智
    • Organizer
      第50回日本呼吸器学会学術講演会
    • Place of Presentation
      京都市(ランチチョンセミナー)
    • Year and Date
      2010-04-25
    • Related Report
      2012 Final Research Report
  • [Presentation] COPD 治療の向上に求められるβ_2 刺激薬の薬理学的特性 COPD の治療戦略―アシストユースの有用性―2010

    • Author(s)
      久米裕昭、東田有智
    • Organizer
      第50回日本呼吸器学会学術講演会
    • Place of Presentation
      京都市(イブニングシンポジウム)
    • Year and Date
      2010-04-24
    • Related Report
      2012 Final Research Report
  • [Presentation] COPD治療の向上に求められるβ_2刺激薬の薬理学的特性2010

    • Author(s)
      久米裕昭
    • Organizer
      第50回日本呼吸器学会学術講演会
    • Place of Presentation
      京都市
    • Year and Date
      2010-04-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 気管支喘息の病態におけるエンドセリン-1 の役割ーあらたな炎症マーカーとしての可能性2010

    • Author(s)
      久米裕昭、辻 清太、牧野 靖、西山 理、東田有智
    • Organizer
      第50回日本呼吸器学会学術講演会
    • Place of Presentation
      京都市
    • Year and Date
      2010-04-23
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [Book] カラー版内科学2012

    • Author(s)
      久米裕昭
    • Total Pages
      2004
    • Publisher
      西村書店
    • Related Report
      2012 Annual Research Report
  • [Book] 気管支拡張薬、総合アレルギー学2011

    • Author(s)
      久米裕昭、東田有智
    • Publisher
      福田 健編 南山堂
    • Related Report
      2012 Final Research Report
  • [Book] β_2 刺激薬 アレルギー疾患イラストレイテッド2010

    • Author(s)
      久米裕昭、牧野 靖、東田有智
    • Publisher
      永倉俊和、福田 寛、足立 満編 メディカルレビュー社
    • Related Report
      2012 Final Research Report
  • [Book] β_2刺激薬、"アレルギー疾患イラストレイテッド"、永倉俊和、他、編2010

    • Author(s)
      久米裕昭, 他
    • Total Pages
      301
    • Publisher
      メディカルレビュー社
    • Related Report
      2010 Annual Research Report
  • [Book] 気管支拡張薬、"総合アレルギー学"福田健編2010

    • Author(s)
      久米裕昭、東田有智
    • Total Pages
      748
    • Publisher
      南山堂
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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