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

• Project/Area Number: 21590977
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kurume 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: ¥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.

Research Products

• [Journal Article] Soluble interleukin-18 receptor complex is a novel biomarker in rheumatoid arthritis (2011)
  • 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
• [Journal Article] Overexpression of chitinase 3-like 1/ykl-40 in lung-specific il-18-transgenic mice, smokers and copd (2011)
  • 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
• [Journal Article] Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias (2011)
  • 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
• [Journal Article] Interleukin-18 and interleukin-18 receptor-alpha expression in allergic asthma (2011)
  • 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
• [Journal Article] Overexpression of chitinase 3-like 1/YKL-40 in lung-specific IL-18-transgenic mice, smokers and COPD (2011)
  • Author(s): Sakazaki, Y., Hoshino, T., 他
  • Journal Title: PLoS One Volume: 6 Issue: 9 Pages: e24177-e24177
  • DOI: 10.1371/journal.pone.0024177
  • Peer Reviewed
• [Journal Article] Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias (2011)
  • Author(s): Okamoto, M., Hoshino, T., 他
  • Journal Title: Eur Respir J Volume: 37 Issue: 5 Pages: 1119-27
  • DOI: 10.1183/09031936.00059810
  • Peer Reviewed
• [Journal Article] Interleukin-18 and interleukin-18 receptor-alpha expression in allergic asthma (2011)
  • Author(s): Imaoka, H., Hoshino, T., 他
  • Journal Title: Eur Respir J Volume: 38 Issue: 4 Pages: 981-3
  • DOI: 10.1183/09031936.00033811
  • Peer Reviewed
• [Journal Article] Exosome secretion of dendritic cells is regulated by hrs, an escrt-0 protein (2010)
  • 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
• [Journal Article] Reference ranges for exhaled nitric oxide fraction in healthy japanese adult population (2010)
  • 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
• [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, 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
• [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
  • 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
  • Peer Reviewed
• [Journal Article] Role of Proinflammatory Cytokine IL-18 and IL-1beta in Bleomycin-induced Lung Injury in Humans and Mice (2009)
  • Author(s): Hoshino T, 他
  • Journal Title: Am J Respir Cell Mol Biol 41 Pages: 661-70
  • 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
• [Presentation] Characteristics of fatal asthma : CD8 positive T cells producing IFN-γ and IL-18 were recruited into small airways in fatal asthma (2009)
  • Author(s): Y.Sakazaki, 他
  • Organizer: European Respiratory Society Annual Congress 2009
  • Place of Presentation: Vienna, Austria
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/imed1/index.html
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/imed1/index.html
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/imedl/index.html
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/imed1/index.html