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Therapy targeting folate receptor beta expressing macrophages in chronic inflammation

Research Project

Project/Area Number 23591441
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKagoshima University

Principal Investigator

MATSUYAMA Takami  鹿児島大学, 医歯(薬)学総合研究科, 教授 (30145479)

Co-Investigator(Kenkyū-buntansha) NAGAI Taku  鹿児島大学, 医歯学総合研究科, 講師 (90363647)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords葉酸リセプター / イムノトキシン / 国際情報交換 / 抗体 / アメリカ合衆国 / マクロファージ
Research Abstract

We assessed the antiarthrogenic and the antifibrotic effects ofdepletion of FRbeta-expressing macrophages in methylated BSA induced arthritis and bleomycin induced skin fibrosis models using a recombinant immunotoxin to FRbeta, respectively. Skin fibrosis was evaluated by the change of skin thickness and hydroxyproline content on Day 29. The TGFbeta1 mRNA levels in the treated skin were assessed by quantitative real-time RT-PCR on Day 9. Anti-FRbeta-PE38 treatment led to a dramatic reduction in the number of FRbeta-expressing macrophages. Additionally, skin thickness and hydroxyproline content, were markedly reduced. TGFbeta1 mRNA levels were also down-regulated after the treatment. TGFbeta1 expression was enriched in FRbeta-expressing macrophages compared with FRbeta-negative macrophages. Anti-FRbeta-PE38 treatment efficiently depleted FRbeta-expressing macrophages and consequently alleviated BLM-induced skin fibrosis.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (20 results)

All 2014 2013 2012

All Journal Article (12 results) (of which Peer Reviewed: 11 results) Presentation (4 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 3 results)

  • [Journal Article] Depletion of folate receptorβ-expressing macrophages alleviates bleomycin-induced experimental skin fibrosis2014

    • Author(s)
      Hua Li, Taku Nagai, Kazuhisa Hasui, Takami Matsuyama
    • Journal Title

      Modern Rheumatology

      Volume: (印刷中)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage uptake and accumulation of folates is polarization-dependent in vitro and in vivo, and is regulated by activin A2014

    • Author(s)
      Rafael Samaniego, Blanca Soler Palacios, Angeles Dominguez-Soto, Carlos Vidal, Azucena Salas, Takami Matsuyama, Carmen Sanchez-Torres, Inmaculada de la Torre, Maria Eugenia Miranda-Carus,Paloma Sanchez-Mateos, and Amaya Puig-Kruger
    • Journal Title

      Journal of Leukocyte Biology

      Volume: (印刷中)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Depletion of folate receptor β-expressing macrophages alleviates bleomycin-induced experimental skin fibrosis.2014

    • Author(s)
      Li H, Nagai T, Hasui K, Matsuyama T.
    • Journal Title

      Modern Rheumatology

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage uptake and accumulation of folates are polarization-dependent in vitro and in vivo and are regulated by activin A.2014

    • Author(s)
      Samaniego R, Palacios BS, Domiguez-Soto A, Vidal C, Salas A, Matsuyama T, Sanchez-Torres C, de la Torre I, Miranda-Caros ME, Sanchez-Mateos P, Puig-Kruger A.
    • Journal Title

      J Leukoc Biol.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles2012

    • Author(s)
      Tsuneyoshi Y, Tanaka M, Nagai T, Sunahara N, Matsuda T, Sonoda T, Ijiri K, Komiya S, Matsuyama T
    • Journal Title

      Scand J Rheumatol

      Volume: 41(2) Pages: 132-40

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of an immunotoxin to folate receptor beta in the intra-articular treatment of antigen-induced arthritis2012

    • Author(s)
      Nagai T, Kyo A, Hasui K, Takao S, Matsuyama T
    • Journal Title

      Arthritis research & therapy

      Volume: 14(3)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel Therapy for Atherosclerosis Using Recombinant Immunotoxin Against Folate Receptorβ―expressing Macrophages2012

    • Author(s)
      Furusho Y, Miyata M, Matsuyama T, Nagai T, Akasaki Y, Hamada N, Miyauchi T, Ikeda Y, Shirasawa T, Ide K, Tei C
    • Journal Title

      Journal of the American Heart Association

      Volume: 1(4)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The Prolyl Hydroxylase PHD3 Identifies Q :1; 2; 3 Proinflammatory Macrophages and its Expression Is Regulated by Activin A2012

    • Author(s)
      Mar´ıa M. Escribese, Elena Sierra-Filardi, Concha Nieto, Rafa Samaniego,†Carmen Sa´nchez-Torres,‡Takami Matsuyama, Elisabeth Calderon-Go´mez, Miguel A. Vega, Azucena Salas,Paloma Sa´nchez-Mateos, and Angel L. Corbı
    • Journal Title

      J Immunol

      Volume: 189(4) Pages: 1946-54

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of an immunotoxin to folate receptor beta in the intra-articular treatment of antigen-induced arthritis.2012

    • Author(s)
      Nagai T, Kyo A, Hasui K, Takao S, Matsuyama T.
    • Journal Title

      Arthritis Res Ther. 2012

      Volume: 14

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The prolyl hydroxylase PHD3 identifies proinflammatory macrophages and its expression is regulated by activin A.2012

    • Author(s)
      Escribese MM, Sierra-Filardi E, Nieto C, Samaniego R, Sánchez-Torres C, Matsuyama T, Calderon-Gómez E, Vega MA, Salas A, Sánchez-Mateos P, Corbí AL.
    • Journal Title

      J Immunol.

      Volume: 189 Pages: 1946-54

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel Therapy for Atherosclerosis Using Recombinant Immunotoxin Against Folate Receptor β-Expressing Macrophages.2012

    • Author(s)
      Furusho Y, Miyata M, Matsuyama T, Nagai T, Li H, Akasaki Y, Hamada N, Miyauchi T, Ikeda Y, Shirasawa T, Ide K, Tei C.
    • Journal Title

      J Am Heart Assoc.

      Volume: 1(4)

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles.2012

    • Author(s)
      Tsuneyoshi Y, Tanaka M, Nagai T, Sunahara N, Matsuda T, Sonoda T, Ijiri K, Komiya S, Matsuyama T.
    • Journal Title

      Scand J Rheumatol.

      Volume: 41(2) Pages: 132-40

    • Related Report
      2011 Research-status Report
  • [Presentation] 葉酸リセプターβ発現マクロファージを標的とした強皮症モデルの治療に関する研究2013

    • Author(s)
      李花、永井拓、松山隆美
    • Organizer
      第57回日本リウマチ学会
    • Place of Presentation
      横浜
    • Year and Date
      2013-04-19
    • Related Report
      2013 Final Research Report
  • [Presentation] The detection of a soluble folate receptor beta in rheumatoid arthritis under anti-TNF therapy2013

    • Author(s)
      永井拓、大坪秀雄、李花、松田剛正、松山隆美
    • Organizer
      第57回日本リウマチ学会
    • Place of Presentation
      横浜
    • Year and Date
      2013-04-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Targeting FR-b-expressing macrophages in inflammatory diseases2012

    • Author(s)
      松山隆美
    • Organizer
      第4回葉酸リセプターとトランスポーターシンポジウム
    • Place of Presentation
      メキシコ
    • Year and Date
      2012-10-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Immunotherapy of antigen-induced rat arthritis with an anti-folate receptor beta Recombinant immunotoxin2012

    • Author(s)
      Taku Nagai, Nobuhiko Sunahara, Takemasa Matsuda, Takami Matsuyama
    • Organizer
      第56回日本リウマチ学会
    • Place of Presentation
      京都
    • Year and Date
      2012-04-27
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 強皮症治療剤2013

    • Inventor(s)
      松山隆美、李花、永井拓
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-054090
    • Filing Date
      2013-03-15
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 軟骨又は骨の破壊の診断薬2012

    • Inventor(s)
      松山隆美、永井拓
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-241968
    • Filing Date
      2012-11-01
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 葉酸リセプターα及びβを認識する抗体2012

    • Inventor(s)
      松山隆美、永井拓、蓮井和久、高尾尊身
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-281525
    • Filing Date
      2012-12-25
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] リコンビナント抗葉酸受容体-βイムノトキシンによる強皮症の治療2012

    • Inventor(s)
      李花、松山隆美、永井拓、蓮井和久
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-281525
    • Filing Date
      2012-12-25
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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