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Molecular mechanisms of airway mucus hypersecretion and airway clearance dynfunction induced by long-acting beta-2 agonist

Research Project

Project/Area Number 23591127
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionTokyo Women's Medical University

Principal Investigator

TAMAOKI Jun  東京女子医科大学, 医学部, 教授 (60147395)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords気道クリアランス / 粘液線毛輸送 / 気道上皮細胞 / 線毛運動 / β2受容体 / 気道上皮 / 細胞増殖 / 粘液分泌 / 喘息 / β2刺激薬 / リモデリング / 上皮成長因子受容体 / ERKカスケード / チロシンリン酸化
Research Abstract

Stimulation of mouse tracheal epithelial cells with the long-acting beta-2 agonist salmeterol increased DNA and protein synthesis in a concentration-dependent manner, an effect that was abolished in the presence of a specific beta-2 receptor antagonist. Salmeterol also induced phosphorylation of EGFR and upregulated the expression of MUC5AC in cultured tracheal epithelial cells, and these effects were significantly inhibited by a EGFR tyrosine kinase inhibitor and transfection of dominant negative mutant of H-Ras, indicating that Ras-ERK cascade may be involved in the salmeterol-induced cell responses. Moreover, salmeterol increased mucociliary transport rate from the carina toward oropharynx in the mouse airway. Ciliary beat frequency of tracheal epithelial cells determined by a photoelectric method was increased in response to salmeterol. These findings suggest that simulation of airway epithelial cells with long-acting beta-2 agonist causes an improvement of airway clearance.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (46 results)

All 2014 2013 2012 2011 Other

All Journal Article (16 results) (of which Peer Reviewed: 8 results) Presentation (26 results) (of which Invited: 7 results) Book (4 results)

  • [Journal Article] 経皮吸収型製剤の位置づけと使い方2014:気管支喘息:気道クリアランス改善に注目して2014

    • Author(s)
      玉置淳
    • Journal Title

      Medicament News

      Volume: 2152 Pages: 12-13

    • Related Report
      2013 Final Research Report
  • [Journal Article] 経皮吸収型製剤の位置づけと使い方2014:気管支喘息:気道クリアランス改善に注目して2014

    • Author(s)
      玉置淳
    • Journal Title

      Medicament News

      Volume: 2152 Pages: 12-13

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 粘液線毛輸送系による気道クリーニング:気道炎症・感染症におけるマクロライドの可能性2013

    • Author(s)
      玉置淳
    • Journal Title

      化学療法の領域

      Volume: 29 Pages: 1542-1554

    • Related Report
      2013 Final Research Report
  • [Journal Article] 喘息・アレルギーと遺伝子Up-To-Date:喘息治療の薬理遺伝学2013

    • Author(s)
      近藤光子,玉置淳
    • Journal Title

      喘息

      Volume: 26 Pages: 42-47

    • Related Report
      2013 Final Research Report
  • [Journal Article] 気管支喘息のphenotype2013

    • Author(s)
      玉置淳
    • Journal Title

      呼吸と循環

      Volume: 61 Pages: 349-355

    • NAID

      40019648700

    • Related Report
      2013 Final Research Report
  • [Journal Article] 粘液線毛輸送系による気道クリーニング:気道炎症・感染症におけるマクロライドの可能性2013

    • Author(s)
      玉置淳
    • Journal Title

      化学療法の領域

      Volume: 29 Pages: 1542-1554

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 医学と医療の最前線:気道分泌の管理と治療2012

    • Author(s)
      近藤光子,玉置淳
    • Journal Title

      日本内科学会雑誌

      Volume: 101 Pages: 3525-3532

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chronic low-grade systemic inflammation causes DNA damage in the lungs of mice2012

    • Author(s)
      Arimura K, Aoshiba K, Tsuji T, Tamaoki J
    • Journal Title

      Lung

      Volume: 190 Pages: 613-620

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diagnosis, evaluation and monitoring of asthma2012

    • Author(s)
      Tamaoki J, Saito H
    • Journal Title

      Allergology International

      Volume: 61 Pages: 351-352

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 慢性気道疾患における咳・痰のリスクと治療:主にCOPD患者の喀痰・咳症状を理解し治療することの意義2012

    • Author(s)
      玉置淳
    • Journal Title

      Therapeutic Research

      Volume: 33 Pages: 897-904

    • Related Report
      2013 Final Research Report
  • [Journal Article] 生物学的製剤を用いた分子標的治療の進歩:重症難治性喘息の治療における生物学製剤の役割2012

    • Author(s)
      玉置淳
    • Journal Title

      東京女子医科大学雑誌

      Volume: 82 Pages: 92-96

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Niflumic acid inhibits goblet cell degranulation in asthma model of guinea pigs2012

    • Author(s)
      Kondo M, Nakata J, Arai N, Izumo T, Takeyama K, Tamaoki J, Nagai A
    • Journal Title

      Allergology International

      Volume: 61 Pages: 133-142

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 生物学製剤を用いた分子標的治療の進歩:重症難治性喘息の治療における生物学製剤の役割2012

    • Author(s)
      玉置淳
    • Journal Title

      東京女子医科大学雑誌

      Volume: 82 Pages: 92-96

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 慢性気道疾患における咳・痰のリスクと治療:主にCOPD患者の喀痰・咳症状を理解し治療することの意義2012

    • Author(s)
      玉置淳
    • Journal Title

      Therapeutic Research

      Volume: 33 Pages: 897-904

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 気道の粘液線毛輸送に対するツロブテロールの効果と作用メカニズムに関する検討2011

    • Author(s)
      玉置淳
    • Journal Title

      アレルギー・免疫

      Volume: 18 Pages: 1530-1539

    • NAID

      40018996763

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 気管支喘息およびCOPDにおける気道粘液分泌亢進の意義2011

    • Author(s)
      玉置淳
    • Journal Title

      Results in Asthma/COPD

      Volume: 10 Pages: 1-6

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] シンポジウム:呼吸器感染症における炎症制御:気道過分泌および粘液線毛輸送の調節2014

    • Author(s)
      玉置淳
    • Organizer
      第54回日本呼吸器学会総会
    • Place of Presentation
      大阪 (日呼吸会誌3 (増刊号): 106)
    • Related Report
      2013 Final Research Report
  • [Presentation] 教育講演:気道クリアランス障害の病態と対策2014

    • Author(s)
      玉置淳
    • Organizer
      第54回日本呼吸器学会総会
    • Place of Presentation
      大阪 (日呼吸会誌3 (増刊号): 81)
    • Related Report
      2013 Final Research Report
  • [Presentation] Role of budesonide/formoterol combination in the treatment of cough variant asthma : comparison with fluticasone monotherapy2014

    • Author(s)
      切士紗織,多賀谷悦子,寺西香織,溝渕莉恵,久保綾子,石井成伸,武山廉,磯野一雄,近藤光子,玉置淳
    • Organizer
      第54回日本呼吸器学会総会
    • Place of Presentation
      大阪 (日呼吸会誌3 (増刊号): 331)
    • Related Report
      2013 Final Research Report
  • [Presentation] モルモット喘息モデルにおけるTransmembrane protein 16Aの発現2014

    • Author(s)
      近藤光子,新井尚希,有村健,中田潤子,多賀谷悦子,武山廉,玉置淳
    • Organizer
      第54回日本呼吸器学会総会
    • Place of Presentation
      大阪 (日呼吸会誌3 (増刊号): 255)
    • Related Report
      2013 Final Research Report
  • [Presentation] Foxc2ノックアウトマウスにおける肺成熟過程の組織学的解析2014

    • Author(s)
      辻真世子,森島正,清水一彦,北原秀治,玉置淳,久米努,江崎太一
    • Organizer
      第119回日本解剖学会総会・全国学術集会
    • Place of Presentation
      宇都宮
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of airway cleaning in inflammatory airway diseases2013

    • Author(s)
      Tamaoki J
    • Organizer
      8th Congress of the Asian Pacific Society of Respirology
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Invited
  • [Presentation] シンポジウム:気道クリアランス:気道における粘液線毛輸送系の制御機構と病態2013

    • Author(s)
      玉置淳
    • Organizer
      第23回日本呼吸ケア・リハビリテーション学会学術集会
    • Place of Presentation
      東京 (日呼ケアリハ学誌23 (Supl): 111S)
    • Related Report
      2013 Final Research Report
  • [Presentation] Chronic low-grade systemic inflammation causes DNA damage in the lungs of mice2013

    • Author(s)
      Arimura K, Aoshiba K, Tsuji T, Tamaoki J
    • Organizer
      European Respiratory Society Annual Meeting 2013
    • Place of Presentation
      Barcelona
    • Related Report
      2013 Final Research Report
  • [Presentation] Symposium : Management of mucus secretion airway diseases : Role of airway hypersecretion in COPD exacerbations2013

    • Author(s)
      Tamaoki J
    • Organizer
      16^<th> Asian Research Symposium in Rhinology
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Final Research Report
  • [Presentation] Symposium : Novel action of macrolide antibiotics : The mechanism of action & future prospects : Regulation of airway clearance in inflammatory ariway diseases2013

    • Author(s)
      Tamaoki J
    • Organizer
      The 28^<th> International Congress of Chemotherapy and Infection
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム:アレルギー疾患治療におけるステロイド薬の標準化:喘息2013

    • Author(s)
      玉置淳
    • Organizer
      第53回日本呼吸器学会総会
    • Place of Presentation
      東京 (日呼吸会誌2(増刊号): 16)
    • Related Report
      2013 Final Research Report
  • [Presentation] 鼻炎合併喘息の病態と治療:one airway, one diseaseの観点から2013

    • Author(s)
      玉置淳
    • Organizer
      第53回日本呼吸器学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Regulation of airway clearance in inflammatory ariway diseases2013

    • Author(s)
      Tamaoki Jun
    • Organizer
      The 28th International Congress of Chemotherapy and Infection
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Management of mucus secretion airway diseases: Role of airway hypersecretion in COPD exacerbations2013

    • Author(s)
      Tamaoki Jun
    • Organizer
      16th Asian Research Symposium in Rhinology
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 気道クリアランス:気道における粘液線毛輸送系の制御機構と病態2013

    • Author(s)
      玉置淳
    • Organizer
      第23回日本呼吸ケア・リハビリテーション学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] COPD患者における粘液の過剰分泌および粘液線毛クリアランスにおけるチオトロピウムの効果2012

    • Author(s)
      多賀谷悦子,切士紗織,新井尚希,奥出梓,難波麻衣,近藤光子,玉置淳
    • Organizer
      第62回日本アレルギー秋季学術大会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] Niflumic acid inhibits antigen- and histamine-induced goblet cell degranulation In a guinea pig asthma model2012

    • Author(s)
      Kondo M, Nakata J, Arai N, Takeyama K, Tagaya E, Tamaoki J, Nagai A
    • Organizer
      Annual Meeting of The American Thoracic Society
    • Place of Presentation
      San Francisco
    • Related Report
      2013 Final Research Report
  • [Presentation] Nagai Effect of tiotropium on mucus hypersecretion and their impact and nasal mucociliary clearance in patients with COPD2012

    • Author(s)
      Tagaya E, Tamaoki J, Kirishi S, Isono K, Nagaoka M, Kimura N, Kondo M
    • Organizer
      Annual Meeting of The American Thoracic Society
    • Place of Presentation
      San Francisco
    • Related Report
      2013 Final Research Report
  • [Presentation] 長時間作用性抗コリン薬とCOPD治療:気管支拡張を超えて:チオトロピウムと気道分泌に関する最新の話題2012

    • Author(s)
      玉置淳
    • Organizer
      第52回日本呼吸器学会総会
    • Place of Presentation
      神戸 (日呼吸会誌1(増刊号): 26)
    • Related Report
      2013 Final Research Report
  • [Presentation] Stimulation of airway mucociliary transport and epithelial ciliary motility by the long acting β2-agonist tulobuterol2011

    • Author(s)
      Nagaoka M, Tamaoki J, Isono K, Kirishi S, Tagaya E, Kondo M, Nagai A
    • Organizer
      Annual Meeting of The American Thoracic Society
    • Place of Presentation
      Denver
    • Related Report
      2011 Research-status Report
  • [Presentation] Strategies for prevention of development to severe and diffucult-to-treat asthma in adults2011

    • Author(s)
      Tamaoki J
    • Organizer
      The 21 st Congress of Interastma/North Asia(招待講演)
    • Place of Presentation
      Gifu
    • Related Report
      2011 Research-status Report
  • [Presentation] Factors influencing development and exacerbations of asthma: Impact of obesity in asthma morbidity and severity2011

    • Author(s)
      Tamaoki J
    • Organizer
      The 16th Congress of the Asian Pacific Society of Respirology(招待講演)
    • Place of Presentation
      Shanghai
    • Related Report
      2011 Research-status Report
  • [Presentation] Effect of tiotropium on mucus hypersecretion and their impact and nasal mucociliary clearance in patients with COPD

    • Author(s)
      Tagaya E, Tamaoki J, Kirishi S, Isono K, Nagaoka M, Kimura N, Kondo M, Nagai A
    • Organizer
      Annual Meeting of The American Thoracic Society
    • Place of Presentation
      San Francisco
    • Related Report
      2012 Research-status Report
  • [Presentation] Niflumic acid inhibits antigen- and histamine-induced goblet cell degranulation In a guinea pig asthma model

    • Author(s)
      Kondo M, Nakata J, Arai N, yakeyama K, Tagaya E, Tamaoki J, Nagai A
    • Organizer
      Annual Meeting of The American Thoracic Society
    • Place of Presentation
      San Francisco
    • Related Report
      2012 Research-status Report
  • [Presentation] チオトロピウムと気道分泌に関する最新の話題

    • Author(s)
      玉置淳
    • Organizer
      第52回日本呼吸器学会総会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 気管支喘息のトータルコントロールをめざして:喘息患者の咳症状に対するLABA/ICS配合剤の臨床効果

    • Author(s)
      玉置淳
    • Organizer
      第52回日本呼吸器学会総会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] The inhibitory effect of niflumic acid on goblet cell degranulation in asthma model of guinea pigs. In : Airway Secretion Research2014

    • Author(s)
      Kondo M, Nakata J, Arai N, Tagaya E, Takeyama K, Tamaoki J (ed, Tamaoki J)
    • Publisher
      Japanese Association for Airway Secretion Research
    • Related Report
      2013 Final Research Report
  • [Book] 風邪症候群と関連疾患:気管・気管支炎,肺炎.ENT臨床フロンティアシリーズ2013

    • Author(s)
      玉置淳,八木理充,落合克律 (小林俊光,高橋晴雄,浦野正美編)
    • Publisher
      中山書店
    • Related Report
      2013 Final Research Report
  • [Book] COPD病態理解のための基礎知識:気道分泌とその障害:慢性閉塞性肺疾患(COPD)のマネジメント改訂3版2013

    • Author(s)
      玉置淳 (橋本修編)
    • Publisher
      医薬ジャーナル社
    • Related Report
      2013 Final Research Report
  • [Book] アレルギー性肺疾患:職業性喘息.医学のあゆみ「呼吸器疾患State of Arts」Ver. 62013

    • Author(s)
      玉置淳 (北村諭,巽浩一郎,石井芳樹編)
    • Publisher
      医歯薬出版
    • Related Report
      2013 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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