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Study for roles of inflammatory cells and cytokines in asthma death, COPD and mouse pulmonary disease models

Research Project

Project/Area Number 21590977
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HOSHINO Tomoaki  久留米大学, 医学部, 教授 (00261066)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords喘息 / COPD / 動物モデル / 炎症細胞 / 気道リモデリング / 炎症性サイトカイン / IL-18
Research Abstract

Background : Eosinophils, CD4+T cells, and Th2 cytokines are thought to contribute to the development of asthma. Recently, a paper reported that pro-inflammatory IL-18 gene polymorphism was significantly associated with the disease severity of bronchial asthma. However, the detail of airway inflammation process in the lungs of nonsmoker asthma death has not reported.
Method : We obtained lung tissues from 12 nonsmokers who died of asthma at autopsy. They died from 1973 to 1998.Lung tissues were also obtained from 5 well-controlled mild asthma patients and 10 nonsmokers who underwent lung cancer extirpation. We examined pulmonary inflammatory cells, and also evaluated the expression of IL-18 and its receptor in the lungs.
Result : The numbers of eosinophils and lymphocytes, but not basophils, nor macrophages were significantly and greatly increased in the lungs when compared with mild asthmatics and nonsmokers. Interestingly, neutrophils were not significantly different when comparing fatal and mild asthmas, but were significantly increased in the lungs of asthma deaths than seen in nonsmokers. CD8+T cells but not CD4+T cells were significantly and greatly increased in the lungs of fatal asthma patients when compared to mild asthmas and nonsmokers. IL-18 proteins were strongly expressed in the bronchoalveolar epithelial cells and pulmonary inflammatory cells in asthma deaths. Moreover, IL-18Rαproteins were enhanced in the pulmonary inflammatory cells, especially CD8+T cells in the lungs of asthma death.
Conclusion : CD8+T cells, eosinophils and over-expressed IL-18 proteins in the lungs may play an important role in the pathogenesis of asthma death.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (19 results)

All 2011 2010 2009 Other

All Journal Article (13 results) (of which Peer Reviewed: 6 results) Presentation (2 results) Remarks (4 results)

  • [Journal Article] Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis2011

    • Author(s)
      Takei S, Hoshino T, Matsunaga K, Sakazaki Y, Sawada M, Oda H, Takenaka SI, Imaoka H, Kinoshita T, Honda S, Ida H, Fukuda TA, Aizawa H
    • Journal Title

      Arthritis research & therapy

      Volume: 13

    • Related Report
      2011 Final Research Report
  • [Journal Article] Overexpression of chitinase 3-like 1/ykl-40 in lung-specific il-18-transgenic mice, smokers and copd2011

    • Author(s)
      Sakazaki Y, Hoshino T, Takei S, Sawada M, Oda H, Takenaka S, Imaoka H, Matsunaga K, Ota T, Abe Y, Miki I, Fujimoto K, Kawayama T, Kato S, Aizawa H
    • Journal Title

      PloS one

      Volume: 6 Pages: 24177-24177

    • Related Report
      2011 Final Research Report
  • [Journal Article] Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias2011

    • Author(s)
      Okamoto M, Hoshino T, Kitasato Y, Sakazaki Y, Kawayama T, Fujimoto K, Ohshima K, Shiraishi H, Uchida M, Ono J, Ohta S, Kato S, Izuhara K, Aizawa H
    • Journal Title

      Eur Respir J

      Volume: 37 Pages: 1119-1127

    • Related Report
      2011 Final Research Report
  • [Journal Article] Interleukin-18 and interleukin-18 receptor-alpha expression in allergic asthma2011

    • Author(s)
      Imaoka H, Gauvreau GM, Watson RM, Smith SG, Dua B, Baatjes AJ, Howie K, Hoshino T, Killian KJ, Aizawa H, O' Byrne PM
    • Journal Title

      Eur Respir J

      Volume: 38 Pages: 981-983

    • Related Report
      2011 Final Research Report
  • [Journal Article] Overexpression of chitinase 3-like 1/YKL-40 in lung-specific IL-18-transgenic mice, smokers and COPD2011

    • Author(s)
      Sakazaki, Y., Hoshino, T., 他
    • Journal Title

      PLoS One

      Volume: 6 Issue: 9 Pages: e24177-e24177

    • DOI

      10.1371/journal.pone.0024177

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias2011

    • Author(s)
      Okamoto, M., Hoshino, T., 他
    • Journal Title

      Eur Respir J

      Volume: 37 Issue: 5 Pages: 1119-27

    • DOI

      10.1183/09031936.00059810

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-18 and interleukin-18 receptor-alpha expression in allergic asthma2011

    • Author(s)
      Imaoka, H., Hoshino, T., 他
    • Journal Title

      Eur Respir J

      Volume: 38 Issue: 4 Pages: 981-3

    • DOI

      10.1183/09031936.00033811

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exosome secretion of dendritic cells is regulated by hrs, an escrt-0 protein2010

    • Author(s)
      Tamai K, Tanaka N, Nakano T, Kakazu E, Kondo Y, Inoue J, Shiina M, Fukushima K, Hoshino T, Sano K, Ueno Y, Shimosegawa T, Sugamura K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 399 Pages: 384-390

    • Related Report
      2011 Final Research Report
  • [Journal Article] Reference ranges for exhaled nitric oxide fraction in healthy japanese adult population2010

    • Author(s)
      Matsunaga K, Hirano T, Kawayama T, Tsuburai T, Nagase H, Aizawa H, Akiyama K, Ohta K, Ichinose M
    • Journal Title

      Allergol Int

      Volume: 59 Pages: 363-367

    • Related Report
      2011 Final Research Report
  • [Journal Article] Elevated levels of thioredoxin 1 in the lungs and sera of idiopathic pulmonary fibrosis, non-specific interstitial pneumonia and cryptogenic organizing pneumonia2010

    • Author(s)
      Iwata Y, Okamoto M, Hoshino T, Kitasato Y, Sakazaki Y, Tajiri M, Matsunaga K, Azuma K, Kawayama T, Kinoshita T, Imaoka H, Fujimoto K, Kato S, Yano H, Aizawa H
    • Journal Title

      Intern Med

      Volume: 49 Pages: 2393-2400

    • NAID

      130000413366

    • Related Report
      2011 Final Research Report
  • [Journal Article] Elevated levels of thioredoxin 1 in the lungs and sera of idiopathic pulmonary fibrosis, non-specific interstitial pneumonia and cryptogenic organizing pneumonia.2010

    • Author(s)
      Iwata Y, 他
    • Journal Title

      Intern Med

      Volume: 49 Pages: 2393-2400

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exosome secretion of dendritic cells is regulated by hrs, an escrt-0 protein.2010

    • Author(s)
      Tamai K, 他
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 399

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of Proinflammatory Cytokine IL-18 and IL-1beta in Bleomycin-induced Lung Injury in Humans and Mice2009

    • Author(s)
      Hoshino T, 他
    • Journal Title

      Am J Respir Cell Mol Biol 41

      Pages: 661-70

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Role of proinflammatory cytokines in respiratory diseases.2010

    • Author(s)
      Hoshino T
    • Organizer
      Joint Meeting of the International Cytokine Society(ICS) and the International Society for Interferon and Cytokine Research (ISICR)
    • Place of Presentation
      Chicago, USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] Characteristics of fatal asthma : CD8 positive T cells producing IFN-γ and IL-18 were recruited into small airways in fatal asthma2009

    • Author(s)
      Y.Sakazaki, 他
    • Organizer
      European Respiratory Society Annual Congress 2009
    • Place of Presentation
      Vienna, Austria
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kurume-u.ac.jp/med/imed1/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.kurume-u.ac.jp/med/imed1/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kurume-u.ac.jp/med/imedl/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.kurume-u.ac.jp/med/imed1/index.html

    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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