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Role of Th17 for persistent lung inflammation in COPD

Research Project

Project/Area Number 20590895
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKyoto 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
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords閉塞性肺疾患 / 動物モデル / COPD / 自己免疫 / Th17炎症 / 喫煙 / 慢性肺疾患 / 獲得免疫 / 慢性閉塞性肺疾患
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.

Report

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

    (37 results)

All 2011 2010 2009 2008 Other

All Journal Article (22 results) (of which Peer Reviewed: 9 results) Presentation (11 results) Book (4 results)

  • [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

    • Related Report
      2010 Final Research Report
  • [Journal Article] Impact of Exacerbations on Emphysema Progression in Chronic Obstructive Pulmonary Disease.2011

    • Author(s)
      Tanabe N, et al.
    • Journal Title

      Am J Respir Crit Care Med.

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2010 Final Research Report
  • [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

    • NAID

      120002511345

    • Related Report
      2010 Final Research Report
  • [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

    • Related Report
      2010 Final Research Report
  • [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: 10-10

    • Related Report
      2010 Final Research Report
  • [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

    • Related Report
      2010 Final Research Report
  • [Journal Article] Lipopolysaccharide induced connective tissue growth factor gene expression in human bronchial epithelial cells.2010

    • Author(s)
      Nishioka M, et al.
    • Journal Title

      Respirology.

      Volume: 15(4) Pages: 669-76

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CT scan findings of emphysema predict mortality in COPD.2010

    • Author(s)
      Haruna A, et al.
    • Journal Title

      Chest.

      Volume: 138(3) Pages: 635-40

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between peripheral airway function and patient-reported outcomes in COPD : a cross-sectional study.2010

    • Author(s)
      Haruna A, et al.
    • Journal Title

      BMC Pulm Med.

      Volume: 10 Pages: 10-10

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Abnormal swallowing reflex and COPD exacerbations.2010

    • Author(s)
      Terada K, et al.
    • Journal Title

      Chest.

      Volume: 137(2) Pages: 326-32

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [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

    • Related Report
      2010 Final Research Report
  • [Journal Article] Protective effect of thioredoxin perfusion but not inhalation in warm ischemic-reperfused rat lungs.2009

    • Author(s)
      Zhang J, Chen F, Nakamura T, Fujinaga T, Aoyama A, Hamakawa H, Sakai H, Hoshino Y, Yodoi J, Wada H, Bando T, Nakamura H.
    • Journal Title

      Redox Rep 14(2)

      Pages: 75-81

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thioredoxin 1 delivery as new therapeutics.2009

    • Author(s)
      Nakamura H, Hoshino Y, Okuyama H, Matsuo Y, Yodoi J.
    • Journal Title

      Adv Drug Deliv Rev 61(4)

      Pages: 303-309

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency.2009

    • Author(s)
      Ahsan MK, Okuyama H, Hoshino Y, Oka S, Masutani H, Yodoi J, Nakamura H.
    • Journal Title

      Antioxid Redox Signal 11(10)

      Pages: 2573-2584

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [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

    • Related Report
      2010 Final Research Report
  • [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

    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [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

    • Related Report
      2010 Final Research Report
  • [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

    • Related Report
      2010 Final Research Report
  • [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

    • Related Report
      2010 Final Research Report
  • [Journal Article] Suppression of choroidal neovascularization by thioredoxin-1 via interaction with complement factor H.2008

    • Author(s)
      Inomata Y, Tanihara H, Tanito M, Okuyama H, Hoshino Y, Kinumi T, Kawaji T, Kondo N, Yodoi J, Nakamura H.
    • Journal Title

      Invest Ophthalmol Vis Sci 49(11)

      Pages: 5118-25

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [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
    • Related Report
      2010 Final Research Report
  • [Presentation] Effects of Thioredoxin-1 on accelerated emphysema progression in cigarette smoke-exposed mice challenged with polyinosine-polycytidylic acid.2010

    • Author(s)
      Tanabe N, et al
    • Organizer
      International Conference of European Respiratory Society
    • Place of Presentation
      Barcelona
    • Year and Date
      2010-09-21
    • Related Report
      2010 Annual Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [Presentation] Distinct responses against polyinosine-polycytidylic acid in smoke-exposed mouse strains with different susceptibility to emphysema2010

    • Author(s)
      Tanabe N, et al
    • Organizer
      International Conference of American Thoracic Society
    • Place of Presentation
      New Orleans
    • Year and Date
      2010-05-18
    • Related Report
      2010 Annual Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [Presentation] COPD Patients' Unmet Needs : The Japanese Experience.2009

    • Author(s)
      Y.Hoshino, M.Mishima
    • Organizer
      The First World Conference of COPD Patients
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2009-06-14
    • Related Report
      2009 Annual Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [Presentation] Systemic Immune Activation by Polyinosine-Polycytidylic Acid Evokes Lung Inflammation Similar to COPD Exacerbation in Cigarette Smoke-Exposed Mice.2009

    • Author(s)
      N.Tanabe, Y.Hoshino, S.Marumo, I.Ito, E.Ogawa, S.Muro, T.Hirai, M.Mishima.
    • Organizer
      2009 International Conference of American Thoracic Society/American Lung Association
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2009-05-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Pathophysiology of Cigarette Smoke Induced Emphysema after Smoking Cessation in a Murine Model.2009

    • Author(s)
      S.Marumo, Y.Hoshino, N.Tanabe, A.Sato, I.Ito, E.Ogawa, S.Muro, T.Hirai, M.Mishima.
    • Organizer
      2009 International Conference of American Thoracic Society/American Lung Association
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2009-05-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] p38 MAPK is a major regulator of cigarette smoke-induced lung inflammation in mice2009

    • Author(s)
      Marumo S, Hoshino Y, et al.
    • Organizer
      American Thoracic Society
    • Place of Presentation
      Toronto
    • Year and Date
      2009-05-17
    • Related Report
      2008 Annual Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [Book] COPD Frontier, March Vol. 8 No. 1 20092009

    • Author(s)
      星野勇馬, 室繁郎, 三嶋理晃
    • Publisher
      メディカルレビュー社
    • Related Report
      2008 Annual Research Report
  • [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
    • Related Report
      2010 Final Research Report
  • [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
    • Related Report
      2010 Final Research Report

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

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