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

2011 Fiscal Year Final Research Report

• 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
• Keywords: 喘息 / COPD / 動物モデル

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 Pages: R52
• [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
• [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] 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
• [Remarks]
  • URL: http://www.med.kurume-u.ac.jp/med/imed1/index.html