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2007 Fiscal Year Final Research Report Summary

Clarification of the underlying mechanism of allergic diseases targeting the signal pathways of the involved cytokines

Research Project

Project/Area Number 18604007
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field アレルギー
Research InstitutionSaga University

Principal Investigator

IZUHARA Kenji  Saga University, Saga Medical School, Dept. Biomol Sciences, Professor (00270463)

Co-Investigator(Kenkyū-buntansha) KANAJI Sachiko  Saga University, Saga Medical School, Dept. Biomol Sciences, Assistant Professor (50363429)
OHTA Shoichiro  Saga University, Saga Medical School, Dept. Biomol Sciences, Assistant Professor (20346886)
SHIRAISHI Hiroshi  Saga University, Saga Medical School, Dept. Biomol Sciences, Assistant Professor (80452837)
NAGAI Hiroichi  Gifu Pharmaceutical University, Dept Pharm, Professor (90082974)
INOUE Makoto  DNAVEC Corp., ベクター開発室, Director (30373541)
Project Period (FY) 2006 – 2007
KeywordsAllergv / Asthma / Gene / Protein / Immunology
Research Abstract

We found in this study that periostin, an extracellular matrix protein, is a component of fibrosis in bronchial asthma and that pendrin, an anion exchanger, is a mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease (COPD). In the former project, we obtained the following results. (1) Upon stimulation of IL-4/IL-13, lung fibroblasts secreted periostin. (2) Periostin was deposited in the fibrotic legions of asthma. (3) Periostin bound to other matrix proteins such as tenascin-C, fibronectin, and collagen V. These results suggest that periostin is secreted from lung fibroblasts stimulated with IL-4/IL-13 in bronchial asthma and is involved in fibrosis of asthma by binding to other matrix proteins. In the latter project, we obtained the following results. (1) Bronchial epithelial cells cultured by the air-interface method in the presence of IL-13 differentiated into mucus-producing cells and these cell expressed pendrin. (2) Expression of pendrin was up-regulated in lung tissues of bronchial asthma and COPD. (3) Enforced expression of pendrin in airway cells caused mucus production. (4) Enforced expression of pendrin into mouse lungs caused mucus production with infiltration of neutrophils. These results suggest that pendrin is induced in the lung tissues of bronchial asthma and COPD and is involved in mucus production in these diseases. Fibrosis and mucus production are deeply correlated with morbidity and mortality of bronchial asthma and COPD. Therefore, the present results are useful to comprehend the whole molecular mechanism of fibrosis and mucus production in bronchial asthma and COPD and to develop therapeutic reagents against these phenotypes.

  • Research Products

    (44 results)

All 2008 2007 2006 Other

All Journal Article (28 results) (of which Peer Reviewed: 14 results) Presentation (13 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Characterization of a patient with atypical amegakaryocytic thrombocytopenia2008

    • Author(s)
      Kanaji S
    • Journal Title

      Eur J Haematol 80

      Pages: 361-364

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Involvement of cysteine protease inhibitors in the defense mechanism against parasites2008

    • Author(s)
      Izuhara K
    • Journal Title

      Med Chem (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease2008

    • Author(s)
      Nakao I
    • Journal Title

      J Immunol (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Characterization of a patient with atypical amegakaryocytic thrombocytopenia.2008

    • Author(s)
      Kanaji, S
    • Journal Title

      Eur J Haematol 80

      Pages: 361-364

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] IL-13 and its signal pathway:Promising targets in the development of atherapeutic agent for bronchial asthma2007

    • Author(s)
      Izuhara K
    • Journal Title

      Curr Signal Transduction Therapy 2・1

      Pages: 31-40

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Effect of IL-13 receptor α2 levels on the biological activity of IL-13 variant R110Q2007

    • Author(s)
      Andrews AL
    • Journal Title

      J Allergy Clin Immunol 120

      Pages: 91-97

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-γ and IL-13 production2007

    • Author(s)
      Hayashi N
    • Journal Title

      Proc Natl Acad Sci USA 104

      Pages: 14765-14770

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Squamous cell carcinoma antigen 1 is an inhibitor of parasite-derived cysteine proteases2007

    • Author(s)
      Kanaji S
    • Journal Title

      FEBS Lett 581

      Pages: 4260-4264

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression of human IL-13 receptor α2 extracellular domain in Pichia pastoris2007

    • Author(s)
      Ohkuri T
    • Journal Title

      Protein Expres Purif 56

      Pages: 48-53

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Analysis of internal motions of interleukin-13 variant associated with severe bronchial asthma using 15N NMR relaxation measurements2007

    • Author(s)
      Yoshida Y
    • Journal Title

      Biochem Biophys Res Commun 358

      Pages: 292-297

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] IL-13 and its signal pathway : Promising targets in the development of a therapeutic agent for bronchial asthma2007

    • Author(s)
      Izuhara, K
    • Journal Title

      Curr Signal Transduction Therapy 2-1

      Pages: 31-40

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of IL-13 receptor α2 levels on the biological activity of IL-13 variant R110Q2007

    • Author(s)
      Andrews, AL
    • Journal Title

      JAllergy Clin Immunol 120-1

      Pages: 91-97

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-Y and IL-13. production2007

    • Author(s)
      Hayashi, N
    • Journal Title

      Proc Natl Acad Sci USA 104-37

      Pages: 14765-14770

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Squamous cell carcinoma antigen 1 is an inhibitor of parasite-derived cysteine proteases2007

    • Author(s)
      Kanaji, S
    • Journal Title

      FEBS Lett 581-22

      Pages: 4260-4264

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of human IL-13 receptor α2 extracellular domain in Pichia pastoris2007

    • Author(s)
      Ohkuri, T
    • Journal Title

      Protein Expr Purif 56-1

      Pages: 48-53

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Analysis of internal motions of interleukin-13 variant associated with severe bronchial asthma using^15N NMR relaxation measurements2007

    • Author(s)
      Yoshida, Y
    • Journal Title

      Biochem Biophys Res Commun 358

      Pages: 292-297

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] IL-13:A promising therapeutic target for bronchial asthma2006

    • Author(s)
      Izuhara K
    • Journal Title

      Curr Med Chem 13・19

      Pages: 2291-2298

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Microarray-based identification of novel biomarkers in asthma2006

    • Author(s)
      Izuhara K
    • Journal Title

      Allergology Int 55・4

      Pages: 361-367

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Involvement of IL-32 in activation-induced cell death in T cells2006

    • Author(s)
      Goda C
    • Journal Title

      Int Immunol 18・2

      Pages: 233-240

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Periostin:A novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals2006

    • Author(s)
      Takayama G
    • Journal Title

      J Allergy Clin Immunol 118・1

      Pages: 98-104

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression of new human inorganic pyrophosphatase in thyroid diseases: Its intimate association with hyperthyroidism2006

    • Author(s)
      Koike E
    • Journal Title

      Biochem Biophys Res Common 341・3

      Pages: 691-696

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] IL-13 : A promising therapeutic target for bronchial asthma.2006

    • Author(s)
      Izuhara, K
    • Journal Title

      Curr Med Chem 13-19

      Pages: 2291-2298

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Microarray-based identification of novel biomarkers in asthma2006

    • Author(s)
      Izuhara, K
    • Journal Title

      Allergology Int 55-4

      Pages: 361-367

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of IL-32 in activation-induced cell death in T cells2006

    • Author(s)
      Goda, C
    • Journal Title

      Int Immunol 18-2

      Pages: 233-240

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Periostin : A novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals2006

    • Author(s)
      Takayama, G
    • Journal Title

      JAllergy Clin Immunol 118-1

      Pages: 98-104

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of new human inorganic pyrophosphatase. in thyroid diseases : Its intimate association with hyperthyroidism2006

    • Author(s)
      Koike, E
    • Journal Title

      Biochem Biophys Res Commun 341-3

      Pages: 691-696

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of cysteine protease inhibitors in the defense mechanism against parasites

    • Author(s)
      Izuhara, K
    • Journal Title

      Med Chem (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease

    • Author(s)
      Nakao, I
    • Journal Title

      J Immunol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Inflammation and allergy drug design and discovery2008

    • Author(s)
      Izuhara K
    • Organizer
      1st International Conference on Drug Design&Discovery
    • Place of Presentation
      ドバイ・アラブ首長国連邦
    • Year and Date
      2008-02-06
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Inflammation and allergy drug design and discovery2008

    • Author(s)
      Izuhara, K
    • Organizer
      1st International Conference on Drug Design & Discovery
    • Place of Presentation
      Dubai, UAE
    • Year and Date
      2008-02-06
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] オーダーメイド医療を目指したアレルギー疾患診断の確立2007

    • Author(s)
      出原 賢治
    • Organizer
      第54回日本臨床検査医学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-23
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] IL-13を基盤としたアレルギー疾患の病態形成機序と治療戦略2007

    • Author(s)
      出原 賢治
    • Organizer
      第57回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京
    • Year and Date
      2007-11-01
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] サイトカインを基盤としたアレルギー性炎症の制御2007

    • Author(s)
      出原 賢治
    • Organizer
      第28回日本炎症・再生医学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-08-03
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] InvoIvement of pendrin, an anion transporter,in mucus hyperproduction of bronchial asthma2007

    • Author(s)
      Izuhara K
    • Organizer
      ICMI2007(13th International Congress of Mucosal Immunology
    • Place of Presentation
      東京・日本
    • Year and Date
      2007-07-12
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Involvement of periostin, an anion transporter in mucus hyperproduction of bronchial asthma2007

    • Author(s)
      Izuhara, K
    • Organizer
      ICMI2007
    • Place of Presentation
      Tokyo, JPN
    • Year and Date
      2007-07-12
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] オーダーメイド医療を目指したアレルギー疾患診断の確立2006

    • Author(s)
      出原 賢治
    • Organizer
      第53回日本臨床検査医学会学術集会
    • Place of Presentation
      弘前
    • Year and Date
      2006-11-11
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] サイトカインを基盤としたアレルギー疾患の病態解析と臨床検査2006

    • Author(s)
      出原 賢治
    • Organizer
      第53回日本臨床検査医学会学術集会
    • Place of Presentation
      弘前
    • Year and Date
      2006-11-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Involvement of pendrin in subepithelial thickening of bronchial asthma downstream of IL-4 and IL-132006

    • Author(s)
      Izuhara K
    • Organizer
      26th Collegium Internationale Allergologicum
    • Place of Presentation
      マルタ島・マルタ共和国
    • Year and Date
      2006-05-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Involvement of pendrin in subepithelial thickening of bronchial asthma downstream of IL-4 and IL-132006

    • Author(s)
      Izuhara, K
    • Organizer
      26th Collegium Internationale Allergologicum 2006
    • Place of Presentation
      Malta
    • Year and Date
      2006-05-09
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Periostin:A novel component of subepithelial thickening of bronchial asthma downstream of IL-4 and IL-13 signals2006

    • Author(s)
      Izuhara K
    • Organizer
      Keystone symposia 2006(Allergy, Allergic Inflammation and Asthma)
    • Place of Presentation
      ブレックンリッジ・米国
    • Year and Date
      2006-04-07
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Periostin : A novel component of subepithelial thickening of bronchial asthma downstream of IL-4 and IL-13 signals2006

    • Author(s)
      Izuhara, K
    • Organizer
      Keystone symposia 2006
    • Place of Presentation
      Breckenridge, USA
    • Year and Date
      2006-04-07
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Immunogenomics and Human Disease2006

    • Author(s)
      Andras Falus
    • Total Pages
      526
    • Publisher
      John Wiley&Sons,Ltd
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Immunogenomics and Human Disease2006

    • Author(s)
      Andras, Falus
    • Total Pages
      526
    • Publisher
      John Wiley & Son Ltd
    • Description
      「研究成果報告書概要(欧文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.biomol.med.saga-u.ac.jp/medbiochem/index.php

URL: 

Published: 2010-02-04  

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