Role of Th17 for persistent lung inflammation in COPD

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590895
• 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: Kyoto University
• Principal Investigator: HOSHINO Yuma Kyoto University, 医学研究科, 助教 (00378746)
• Co-Investigator(Kenkyū-buntansha): MURO Shigeo 京都大学, 医学研究科, 講師 (60344454) ; ITO Isao 京都大学, 医学研究科, 助教 (40447975)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Hajime 田附興風会北野病院, 健診部長 (70303914)
• Project Period (FY): 2008 – 2010
• Keywords: 閉塞性肺疾患 / 動物モデル

Research Abstract

Involvement ofTh17 in the persistent neutrophil inflammation in COPD was examined using a mouse model of cigarette smoke-induced emphysema. Smoke exposure upregulated mRNA expression of interleukin-17 and increaesd Th17 cells in the lungs and spleen of "smoke-susceptible" mouse strain but not in those of "smoke-resistant" strain. To explore mechanisms of the Th17 induction by cigarette smoke, naive mice were sensitized with lung-lysate of smoke-exposed mice and challaged with cigarette smoke itself. The sensitization, however, was not sufficient for Th17 induction. We then examined adaptive transfer of splenic cells or bone marrow-derived dendritic cell exposed to cigarette smoke extract-treated lung lysate in advance. The adaptive transfer of the immune cells, however, did not induce Th17 response in the lungs of smoke-challanged mice. In conclusion, Th17 was indeed induced by cigarette smoking in mice and was related to disease susceptibility. Further studies are required to prove causal relationship between Th17 and emphysema progression.

Research Products

• [Journal Article] Impact of Exacerbations on Emphysema Progression in Chronic Obstructive Pulmonary Disease. (2011)
  • Author(s): Tanabe N, Muro S, Hirai T, Oguma T, Terada K, Marumo S, Kinose D, Ogawa E, Hoshino Y, Mishima M.
  • Journal Title: Am J Respir Crit Care Med
• [Journal Article] Abnormal swallowing reflex and COPD exacerbations. (2010)
  • Author(s): Terada K, Muro S, Ohara T, Kudo M, Ogawa E, Hoshino Y, Hirai T, Niimi A, Chin K, Mishima M.
  • Journal Title: Chest 137(2) Pages: 326-32
• [Journal Article] Age-related changes in the trachea in healthy adults. (2010)
  • Author(s): Sakai H, Nakano Y, Muro S, Hirai T, Takubo Y, Oku Y, Hamakawa H, Takahashi A, Sato T, Chen F, Sahara H, Fujinaga T, Sato K, Sonobe M, Shoji T, Miyahara R, Okubo K, Bando T, Hirata T, Date H, Mishima M.
  • Journal Title: Adv Exp Med Biol 662 Pages: 115-20
• [Journal Article] Lipopolysaccharide induced connective tissue growth factor gene expression in human bronchial epithelial cells. (2010)
  • Author(s): Nishioka M, Ogawa E, Kinose D, Haruna A, Ohara T, Ito I, Hoshino Y, Ito Y, Matsumoto H, Niimi A, Mio T, Chin K, Hirai T, Muro S, Mishima M.
  • Journal Title: Respirology 15(4) Pages: 669-76
• [Journal Article] Relationship between peripheralairway function and patient-reported outcomes in COPD : a cross-sectional study. (2010)
  • Author(s): Haruna A, Oga T, Muro S, Ohara T, Sato S, Marumo S, Kinose D, Terada K, Nishioka M, Ogawa E, Hoshino Y, Hirai T, Chin K, Mishima M.
  • Journal Title: BMC Pulm Med 10 Pages: 10
• [Journal Article] CT scan findings of emphysema predict mortality in COPD. (2010)
  • Author(s): Haruna A, Muro S, Nakano Y, Ohara T, Hoshino Y, Ogawa E, Hirai T, Niimi A, Nishimura K, Chin K, Mishima M.
  • Journal Title: Chest 138(3) Pages: 635-40
• [Journal Article] Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency. (2009)
  • Author(s): Terada K, Muro S, Ohara T, Haruna A, Marumo S, Kudo M, Ogawa E, Hoshino Y, Hirai T, Niimi A, Mishima M.
  • Journal Title: Respirology 14(8) Pages: 1151-5
• [Journal Article] Body mass index in male patients with COPD : correlation with low attenuation areas on CT. (2009)
  • Author(s): Ogawa E, Nakano Y, Ohara T, Muro S, Hirai T, Sato S, Sakai H, Tsukino M, Kinose D, Nishioka M, Niimi A, Chin K, Pare PD, Mishima M.
  • Journal Title: Thorax 64(1) Pages: 20-5
• [Journal Article] Impact of gastro-oesophageal reflux disease symptoms on COPD exacerbation. (2008)
  • Author(s): Terada K, Muro S, Sato S, Ohara T, Haruna A, Marumo S, Kinose D, Ogawa E, Hoshino Y, Niimi A, Terada T, Mishima M.
  • Journal Title: Thorax 63(11) Pages: 951-5
• [Journal Article] Thioredoxin-1 ameliorates cigarette smoke-induced lung inflammation and emphysema in mice. (2008)
  • Author(s): Sato A, Hoshino Y, Hara T, Muro S, Nakamura H, Mishima M, Yodoi J.
  • Journal Title: J Pharmacol Exp Ther 325(2) Pages: 380-8
• [Journal Article] Longitudinal study of airway dimensions in chronic obstructive pulmonary disease using computed tomography. (2008)
  • Author(s): Ohara T, Hirai T, Sato S, Terada K, Kinose D, Haruna A, Marumo S, Nishioka M, Ogawa E, Nakano Y, Hoshino Y, Ito Y, Matsumoto H, Niimi A, Mio T, Chin K, Muro S, Mishima M.
  • Journal Title: Respirology 13(3) Pages: 372-8
• [Journal Article] Relationship between pulmonary emphysema and osteoporosis assessed by CT in patients with COPD. (2008)
  • Author(s): Ohara T, Hirai T, Muro S, Haruna A, Terada K, Kinose D, Marumo S, Ogawa E, Hoshino Y, Niimi A, Chin K, Mishima M.
  • Journal Title: Chest 134(6) Pages: 1244-9
• [Journal Article] Redox-based therapeutics for lung diseases. (2008)
  • Author(s): Hoshino Y, Mishima M.
  • Journal Title: Antioxid Redox Signal 10(4) Pages: 701-4
• [Presentation] Animal Model Of Cigarette Smoke Induced Airway Disease Without Emphysema In Mice And Effect Of Dexamethasone On It. (2011)
  • Author(s): Kiyokawa H, Hoshino Y, Tanabe N, Marumo S, Ogawa E, Muro S, Hirai T, Mishima M.
  • Organizer: 2011 International Conference of American Thoracic Society.
  • Place of Presentation: Denver
  • Year and Date: 2011-05-16
• [Presentation] Distinct Responses Against Polyinosine-Polycytidylic Acid In Smoke-Exposed Mouse Strains With Different Susceptibility To Emphysema. (2010)
  • Author(s): Tanabe N, Hoshino Y, Kiyokawa H, Marumo S, Ogawa E, Muro S, Hirai T, Mishima M.
  • Organizer: 2010 International Conference of American Thoracic Society.
  • Place of Presentation: New Orleans.
  • Year and Date: 2010-05-18
• [Presentation] COPD Patients' Unmet Needs : The Japanese Experience. (2009)
  • Author(s): Hoshino Y, Mishima M.
  • Organizer: First World Conference of COPD Patients. A Global Mandate for COPD Care.
  • Place of Presentation: Rome
  • Year and Date: 2009-06-14
• [Presentation] Pathophysiology of cigarette smoke induced emphysema after smoking cessation in a murine model. (2009)
  • Author(s): Marumo S, Hoshino Y, Tanabe N, Sato A, Ito I, Ogawa E, Muro S, Hirai T, Mishima M.
  • Organizer: 2009 International Conference of American Thoracic Society
  • Place of Presentation: San Diego.
  • Year and Date: 2009-05-17
• [Presentation] Systemic immune activation by polyinosine-polycytidylic acid evokes lung inflammation similar to COPD exacerbation in smoke-exposed mice. (2009)
  • Author(s): Tanabe N, Hoshino Y, Marumo S, Ito I, Ogawa E, Muro S, Hirai T, Mishima M.
  • Organizer: 2009 International Conference of American Thoracic Society
  • Place of Presentation: San Diego.
  • Year and Date: 2009-05-17
• [Book] 疾患の病因と病態COPD P38MAPK inhibitor.Annual Review呼吸器 (2010)
  • Author(s): 室繁郎, 星野勇馬, 三嶋理晃
  • Total Pages: 68-73
• [Book] 【COPD新ガイドラインで期待される予防と治療】慢性安定期の診療慢性安定期の治療.治療学;43(9)
  • Author(s): 室繁郎, 小川恵美子, 星野勇馬, 三嶋理晃
  • Total Pages: 947-952
• [Book] 【薬物療法の新展開】薬物療法の未来COPDの新規治療薬.COPD FRONTIER;8(1)
  • Author(s): 星野勇馬, 室繁郎, 三嶋理晃
  • Total Pages: 93-99