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Pathogenesis of airway inflammation in refractory asthma.

Research Project

Project/Area Number 20591191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionSaitama Medical University

Principal Investigator

NAGATA Makoto  Saitama Medical University, 医学部, 教授 (20211443)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアレルギー / 重症喘息 / 好球 / 好酸球 / Th1 / TXB2 / IP-10 / 好中球性炎症Interleukin-8 / Tumor necrosis factor-α / Interleukin-13 / β2受容体刺激薬 / 吸入ステロイド薬 / 好中球 / Interleukin-8 / Interferon-γ / Interferon-β
Research Abstract

In the pathogenesis of severe asthma, not only eosinophils but also neutrophils play important roles. We previously reported a positive correlation between the concentrations of neutrophils and eosinophils in induced sputum from patients with severe, corticosteroid-dependent asthma. Furthermore, we reported that, even in the absence of chemoattractant for eosinophils, neutrophils stimulated by IL-8 are capable of inducing the trans-basement membrane migration of eosinophils, suggesting that IL-8-stimulated neutrophils lead eosinophils to accumulate in the airways of asthmatic patients. In this study, we further elucidated the pathogenesis of airway inflammation in refractory asthma. We found that concentrations of IL-8 in induced sputa are higher in severe asthmatics than in mild asthmatics. Further, concentrations of TXB2 or LTB4 in EBC also increased in unstable or severe asthma. IFNs augment eosinophil adhesion-inducing activity of endotherial cells. Salbutamol increases IL-13 and decreases IFN-γ production by mononuclear cells from allergic asthmatics. Finally, CXCR3 ligands including IP-10 increase adhesiveness and superoxide anion production of eosinophils. These findings are thought to play important roles in the pathogenesis of severe asthma.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (62 results)

All 2010 2009 2008

All Journal Article (12 results) (of which Peer Reviewed: 11 results) Presentation (49 results) Book (1 results)

  • [Journal Article] Changes in airway inflammation and hyperresponsiveness after inhaled corticosteroid cessation in allergic asthma.2010

    • Author(s)
      Takaku Y, Nakagome K, Kobayashi T, Yamaguchi T, Nishihara F, Soma T, Hagiwara K, Kanazawa M, Nagata M.
    • Journal Title

      Int Arch Allergy Immunol 152 S(1)

      Pages: 41-46

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Salbutamol modulates the balance of Th1 and Th2 cytokines by mononuclear cells from allergic asthmatics.2010

    • Author(s)
      Yamaguchi T, Soma T, Takaku Y, Nakagome K, Hagiwara K, Kanazawa M, Nagata M.
    • Journal Title

      Int Arch Allergy Immunol 152 S(1)

      Pages: 32-40

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Salbutamol modulates the balance of Th1 and Th2 cytokines by mononuclear cells from allergic asthmatics.2010

    • Author(s)
      Yamaguchi T, et al
    • Journal Title

      Int Arch Allergy Immunol.

      Volume: 152 Pages: 32-40

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in airway inflammation and hyperresponsiveness after inhaled corticosteroid cessation in allergic asthma2010

    • Author(s)
      Takaku, Y
    • Journal Title

      Int Arch Allergy Immunol 150(In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophilic inflammation and CXC chemokines in patients with refractory asthma.2009

    • Author(s)
      Kikuchi S, Kikuchi I, Takaku Y, Kobayashi T, Hagiwara K, Kanazawa M, Nagata M.
    • Journal Title

      Int Arch Allergy Immunol 149 S(1)

      Pages: 87-93

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Eosinophil superoxide anion generation induced by adhesion molecules and leukotriene D42009

    • Author(s)
      Mori M, Takaku Y, Kobayashi T, Hagiwara K, Kanazawa M, Nagata M.
    • Journal Title

      Int Arch Allergy Immunol 149 S(1)

      Pages: 31-38

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophilic inflammation and CXC chemokines in patients with refractory asthma. Int Arch Allergy Immunol2009

    • Author(s)
      Kikuchi S
    • Journal Title

      Int Arch Allergy Immunol. 149

      Pages: 87-93

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eosinophil superoxide anion generation induced by adhesion molecules and leukotriene D42009

    • Author(s)
      Mori M
    • Journal Title

      Int Arch Allergy Immunol. 149

      Pages: 31-38

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 炎症病態2009

    • Author(s)
      杣知行
    • Journal Title

      喘息 21

      Pages: 32-38

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Interferon-beta augments eosinophil adhesion-inducing activity of endothelial cells.2008

    • Author(s)
      Kobayashi T, Takaku Y, Yokote A, Miyazawa H, Soma T, Hagiwara K, Kanazawa M, Nagata M.
    • Journal Title

      Eur Respir J. 32

      Pages: 1540-1547

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effect of budesonide alone and in combination with formoterol on IL-5 and RANTES production from mononuclear cells.2008

    • Author(s)
      Soma T, Takaku Y, Kobayashi T, Hagiwara K, Kanazawa M, Uematsu K, Nagata M.
    • Journal Title

      Int Arch Allergy Immunol 146 S(1)

      Pages: 22-27

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interferon-β augments eosinophil adhesion-inducing activity of endot helial cells.2008

    • Author(s)
      T. kobayashi
    • Journal Title

      Eur Respir J 32

      Pages: 1540-1547

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Effect of Omalizumab in Japanese severe allergic asthma and rhinitis.2010

    • Author(s)
      西原冬実
    • Organizer
      WAO International Scientific Conference
    • Place of Presentation
      UAE.
    • Year and Date
      2010-12-06
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞生物学からみたICS/LABA 配合剤2010

    • Author(s)
      永田真
    • Organizer
      第60回日本アレルギー学会秋季学術大会教育セミナー1
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-25
    • Related Report
      2010 Final Research Report
  • [Presentation] OVA 惹起好中球性気道炎症モデルにおける,ドーパミンD1 受容体拮抗薬の抑制効果2010

    • Author(s)
      中込一之
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-25
    • Related Report
      2010 Final Research Report
  • [Presentation] 急性好酸球性肺炎の気管支肺胞洗浄液におけるサイトカイン・ケモカイン濃度の解析2010

    • Author(s)
      中込一之
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-25
    • Related Report
      2010 Final Research Report
  • [Presentation] 成人重症喘息患者における好中球性気道炎症に対する喘息教育効果の検討2010

    • Author(s)
      高久洋太郎
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-25
    • Related Report
      2010 Final Research Report
  • [Presentation] 気管支喘息患者における吸入ステロイド中止の好中球性炎症関連分子への影響2010

    • Author(s)
      高久洋太郎
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-25
    • Related Report
      2010 Final Research Report
  • [Presentation] ロイコトリエン受容体拮抗薬の単核球サイトカイン産生に及ぼす影響2010

    • Author(s)
      西原冬実
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京都
    • Year and Date
      2010-11-25
    • Related Report
      2010 Final Research Report
  • [Presentation] 細胞生物学からみたICS/LABA配合剤2010

    • Author(s)
      永田真
    • Organizer
      第60回日本アレルギー学会秋季学術大会教育セミナー
    • Place of Presentation
      東京国際フォーラム東京都
    • Year and Date
      2010-11-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Neutrophilc inflammation in severe asthma. Symposium 10: Immunology of Allergy and Asthma.2010

    • Author(s)
      永田真
    • Organizer
      The 8th Asia Pacific Congress of Allergy, Asthma and Clinical Immunology
    • Place of Presentation
      Singapore
    • Year and Date
      2010-11-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Effect of Omalizumab in Japanese severe allergic asthma.2010

    • Author(s)
      西原冬実
    • Organizer
      The 8th Asia Pacific Congress of Allergy, Asthma and Clinical Immunology
    • Place of Presentation
      Singapore
    • Year and Date
      2010-11-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Salbutamol modulates the balance of Th1 and Th2 cytokines by mononuclear cells from allergic asthmatics.2010

    • Author(s)
      山口剛史
    • Organizer
      The 8th Asia Pacific Congress of Allergy, Asthma and Clinical Immunology
    • Place of Presentation
      Singapore
    • Year and Date
      2010-11-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Neutrophilc inflammation in severe asthma2010

    • Author(s)
      Nagata M
    • Organizer
      The 8th Asia Pacific Congress of Allergy, Asthma and Clinical Immunology
    • Place of Presentation
      Singapore
    • Year and Date
      2010-11-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] 喘息長期管理の今後の課題2010

    • Author(s)
      永田真
    • Organizer
      第20回国際喘息学会日本北アジア部会モーニングセミナー
    • Place of Presentation
      東京都
    • Year and Date
      2010-07-03
    • Related Report
      2010 Final Research Report
  • [Presentation] 喘息長期管理の今後の課題2010

    • Author(s)
      永田真
    • Organizer
      第20回国際喘息学会日本北アジア部会モーニングセミナー
    • Place of Presentation
      京王プラザホテル東京都
    • Year and Date
      2010-07-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 低用量吸入ステロイドによりコントロールされた成人喘息患者における治療中止の検討2010

    • Author(s)
      高久洋太郎
    • Organizer
      第20回国際喘息学会日本北アジア部会
    • Place of Presentation
      東京都
    • Year and Date
      2010-07-02
    • Related Report
      2010 Final Research Report
  • [Presentation] 埼玉医大アレルギーセンターにおける抗IgE 抗体療法導入8 症例の臨床的検討2010

    • Author(s)
      西原冬実
    • Organizer
      第22回日本アレルギー学会春季臨床大会
    • Place of Presentation
      京都
    • Year and Date
      2010-05-08
    • Related Report
      2010 Final Research Report
  • [Presentation] 成人喘息患者の気道炎症に対する喘息教育効果の検討2010

    • Author(s)
      高久洋太郎
    • Organizer
      第22回日本アレルギー学会春季臨床大会
    • Place of Presentation
      京都
    • Year and Date
      2010-05-08
    • Related Report
      2010 Final Research Report
  • [Presentation] 気管支喘息における炎症性サイトカイン産生に及ぼすサルブタモールの影響2010

    • Author(s)
      山口剛史
    • Organizer
      第50回日本呼吸器学会
    • Place of Presentation
      京都
    • Year and Date
      2010-04-24
    • Related Report
      2010 Final Research Report
  • [Presentation] 喘息:長時間作用型β2刺激薬2010

    • Author(s)
      永田真
    • Organizer
      第50回日本呼吸器学会シンポジウム大規模臨床試験より見えること
    • Place of Presentation
      東京都
    • Year and Date
      2010-04-24
    • Related Report
      2010 Final Research Report
  • [Presentation] 喘息長期管理の今後の課題2010

    • Author(s)
      永田真
    • Organizer
      第50回日本呼吸器学会シンポジウム
    • Place of Presentation
      東京国際フォーラム東京都
    • Year and Date
      2010-04-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] ダニ・アレルギー患者由来単核球における好中球性炎症関連分子の検討2010

    • Author(s)
      高久洋太郎
    • Organizer
      第50回日本呼吸器学会
    • Place of Presentation
      京都
    • Year and Date
      2010-04-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 好中球性炎症の関与2010

    • Author(s)
      永田真, 杣知行
    • Organizer
      第50回日本呼吸器学会シンポジウム気管支喘息の病態の新知見
    • Place of Presentation
      東京都
    • Year and Date
      2010-04-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 長時間作用型β2刺激薬2010

    • Author(s)
      永田真
    • Organizer
      第50回日本呼吸器学会シンポジウム
    • Place of Presentation
      東京国際フォーラム東京都
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Changes in airway inflammation and hyperresponsiveness following cessation of inhaled corticosteroid in asthma.2010

    • Author(s)
      高久洋太郎
    • Organizer
      American Academy of Allergy Asthma & Innumology 2010 Annual Meeting.
    • Place of Presentation
      New Orleans
    • Year and Date
      2010-03-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Theophylline attenuates eosinophil adhesion to Interferon IFN-gamma-stimulated endothelial cells.2010

    • Author(s)
      Soma T.
    • Organizer
      American Academy of Allergy Asthma & Innumology 2010 Annual Meeting.
    • Place of Presentation
      New Orleans
    • Year and Date
      2010-03-01
    • Related Report
      2010 Final Research Report
  • [Presentation] 重症喘息の病態と治療2010

    • Author(s)
      永田真
    • Organizer
      第18回小児臨床薬理・アレルギー・免疫研究会ランチョンセミナー
    • Place of Presentation
      四日市ホテル三重県
    • Year and Date
      2010-01-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] Effects of β2-agonist on the Productions of Th1 and Th2 Cytokines by Mononuclear Cells from Patients with Asthma.2009

    • Author(s)
      山口剛史
    • Organizer
      The XXI World Allergy Congress
    • Place of Presentation
      Buenos Aires
    • Year and Date
      2009-12-08
    • Related Report
      2010 Final Research Report
  • [Presentation] CXCR3 ligands upregulate the effector functions of eosinophils.2009

    • Author(s)
      高久洋太郎
    • Organizer
      The XXI World Allergy Congress
    • Place of Presentation
      Buenos Aires
    • Year and Date
      2009-12-07
    • Related Report
      2010 Final Research Report
  • [Presentation] 免疫療法の位置づけと展望2009

    • Author(s)
      永田真
    • Organizer
      第59回日本アレルギー学会学術大会委員会企画ワークショップ
    • Place of Presentation
      秋田キャッスルホテル秋田市
    • Year and Date
      2009-10-31
    • Related Report
      2009 Annual Research Report
  • [Presentation] イブニングシンポジウム:重症気管支喘息への取り組み.「重症喘息の炎症病態」2009

    • Author(s)
      永田真
    • Organizer
      第59回日本アレルギー学会学術大会
    • Place of Presentation
      秋田市
    • Year and Date
      2009-10-30
    • Related Report
      2010 Final Research Report
  • [Presentation] 気管支喘息患者における呼気凝縮液中エイコサノイドの検討2009

    • Author(s)
      高久洋太郎
    • Organizer
      第58回日本アレルギー学会秋季学術大会
    • Place of Presentation
      秋田市
    • Year and Date
      2009-10-30
    • Related Report
      2010 Final Research Report
  • [Presentation] 寛解した気管支喘息患者におけるTh1/Th2 インバランスからみた吸入ステロイド中止後の病状推移の検討2009

    • Author(s)
      高久洋太郎
    • Organizer
      第58回日本アレルギー学会秋季学術大会
    • Place of Presentation
      秋田市
    • Year and Date
      2009-10-30
    • Related Report
      2010 Final Research Report
  • [Presentation] 重症喘息の炎症病態2009

    • Author(s)
      永田真
    • Organizer
      第59回日本アレルギー学会学術大会イブニングシンポジウム:重症気管支喘息への取り組み
    • Place of Presentation
      秋田キャッスルホテル秋田市
    • Year and Date
      2009-10-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] ダニ・アレルギー患者由来単核球における好中球性炎症関連分子の検討2009

    • Author(s)
      高久洋太郎
    • Organizer
      第58回日本アレルギー学会秋季学術大会
    • Place of Presentation
      秋田市
    • Year and Date
      2009-10-29
    • Related Report
      2010 Final Research Report
  • [Presentation] サルブタモールのアレルギー性気道炎症におけるTh1/Th2 サイトカイン産生への効果2009

    • Author(s)
      山口剛史
    • Organizer
      第19回国際喘息学会日本北アジア部会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-10
    • Related Report
      2010 Final Research Report
  • [Presentation] CXCR3 リガンドは好酸球の接着反応と活性酸素産生を誘導する2009

    • Author(s)
      高久洋太郎
    • Organizer
      第19回国際喘息学会日本北アジア部会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 喘息における吸入ステロイド中止可能症例の臨床的検討2009

    • Author(s)
      高久洋太郎
    • Organizer
      第50回日本呼吸器学会学術講演会
    • Place of Presentation
      東京都
    • Year and Date
      2009-06-14
    • Related Report
      2010 Final Research Report
  • [Presentation] 新しい喘息治療のアプローチ2009

    • Author(s)
      中込一之
    • Organizer
      第49回日本呼吸器学会学術講演会教育イブニングシンポジウム「喘息治療に残された課題は?」
    • Place of Presentation
      東京都
    • Year and Date
      2009-06-13
    • Related Report
      2010 Final Research Report
  • [Presentation] IFN-γ による血管内皮細胞の好酸球接着増強に及ぼすテオフィリンの効果2009

    • Author(s)
      杣知行
    • Organizer
      第50回日本呼吸器学会学術講演会
    • Place of Presentation
      東京都
    • Year and Date
      2009-06-13
    • Related Report
      2010 Final Research Report
  • [Presentation] 気管支喘息患者における呼気凝縮液中エイコサノイドの検討2009

    • Author(s)
      高久洋太郎
    • Organizer
      第50回日本呼吸器学会学術講演会
    • Place of Presentation
      日東京都
    • Year and Date
      2009-06-12
    • Related Report
      2010 Final Research Report
  • [Presentation] 制御性T 細胞と免疫・アレルギー疾患2009

    • Author(s)
      永田真
    • Organizer
      第49回日本呼吸器学会学術講演会教育講演1
    • Place of Presentation
      東京都
    • Year and Date
      2009-06-12
    • Related Report
      2010 Final Research Report
  • [Presentation] 米国ガイドラインEPR3 の喘息管理の考え方2009

    • Author(s)
      永田真
    • Organizer
      第49回日本呼吸器学会学術講演会ランチョンセミナー2
    • Place of Presentation
      東京都
    • Year and Date
      2009-06-12
    • Related Report
      2010 Final Research Report
  • [Presentation] 制御性T細胞と免疫・アレルギー疾患2009

    • Author(s)
      永田真
    • Organizer
      第49回日本呼吸器学会学術講演会教育講演
    • Place of Presentation
      東京国際フォーラム東京都
    • Year and Date
      2009-06-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] 米国ガイドラインEPR3の喘息管理の考え方2009

    • Author(s)
      永田真
    • Organizer
      第49回日本呼吸器学会学術講演会ランチョン講演
    • Place of Presentation
      東京国際フォーラム東京都
    • Year and Date
      2009-06-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] 吸入ステロイドは喘息の進行を抑えるか2009

    • Author(s)
      永田真
    • Organizer
      Con の立場から.第21 回日本アレルギー学会春季臨床大会Pro Con
    • Place of Presentation
      岐阜市
    • Year and Date
      2009-06-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 吸入ステロイドは喘息の進行を抑えるかCon2009

    • Author(s)
      永田真
    • Organizer
      第21回日本アレルギー学会春季臨床大会 Pro Con
    • Place of Presentation
      長良川国際会議場岐阜市
    • Year and Date
      2009-06-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] アレルゲン免疫療法の進歩と展望2009

    • Author(s)
      永田真
    • Organizer
      第21回日本アレルギー学会春季臨床大会シンポジウム「アレルギーの免疫療法と抗体療法」
    • Place of Presentation
      岐阜市
    • Year and Date
      2009-06-04
    • Related Report
      2010 Final Research Report
  • [Presentation] アレルゲン免疫療法の進歩と展望2009

    • Author(s)
      永田真
    • Organizer
      第21回日本アレルギー学会春季臨床大会シンポジウム「アレルギーの免疫療法と抗体療法」
    • Place of Presentation
      長良川国際会議場岐阜市
    • Year and Date
      2009-06-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] New aspects of airway inflammation in severe asthma.2008

    • Author(s)
      Makoto Nagata
    • Organizer
      The 19^<th> INTERASMA Japan-North Asia ( Invited lecture)
    • Place of Presentation
      大阪市
    • Year and Date
      2008-07-11
    • Related Report
      2008 Annual Research Report
  • [Book] 難治性喘息と気道炎症・リモデリング : 炎症細胞. 難治性喘息をめぐって. 森川昭博他編集.2009

    • Author(s)
      永田真
    • Total Pages
      5
    • Publisher
      ライフサイエンス出版
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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