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Function of cyclophilin A and CD147 in rheumatoid arthritis

Research Project

Project/Area Number 23790311
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionFukuoka University

Principal Investigator

NISHIOKU Tsuyoshi  福岡大学, 薬学部, 助教 (90435115)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsCypA / CD147 / 関節リウマチ / シクロフィリンA
Research Abstract

Cyclophilin A (CypA), a member of the immunophilin family, is a ubiquitously distributed intracellular protein. Recent studies have shown that CypA is secreted by cells in response to inflammatory stimuli. Elevated levels of extracellular CypA and its receptor, CD147 have been detected in the synovium of patients with RA. However, the precise process of interaction between CypA and CD147 in the development of RA remains unclear. This study aimed to investigate CypA secretion from fibroblast-like synoviocytes (FLS) isolated from mice with collagen-induced arthritis (CIA) and CypA-induced CD147 expression in mouse macrophages. Both CypA and CD147 were highly expressed in the joints of CIA mice. CD147 was expressed in the infiltrated macrophages in the synovium of CIA mice. In vitro, spontaneous CypA secretion from FLS was detected and this secretion was increased by stimulation with LPS. CypA markedly increased CD147 levels in macrophages. These findings suggest that an interaction in the synovial joints between extracellular CypA and CD147 expressed by macrophages forms one of the critical mechanisms underlying RA pathogenesis.

Report

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

    (21 results)

All 2013 2012 2011 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (12 results)

  • [Journal Article] Cyclophilin A secreted from fibroblast-like synoviocytes is involved in the induction of CD147 expression in macrophages of mice with collagen-induced arthritis.2012

    • Author(s)
      Nishioku T, Dohgu S, Koga M, Machida T, Watanabe T, Miura T, Tsumagari K, Terasawa M, Yamauchi A, Kataoka Y.
    • Journal Title

      J Inflamm (Lond)

      Volume: 9(1) Issue: 1 Pages: 44-44

    • DOI

      10.1186/1476-9255-9-44

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Atorvastatin stimulates neuroblastoma cells to induce neurite outgrowth by increasing cellular prion protein expression.2012

    • Author(s)
      Watanabe T, Yasutaka Y, Nishioku T, Nakashima A, Futagami K, Yamauchi A, Kataoka Y.
    • Journal Title

      Neurosci Lett

      Volume: 531(2) Issue: 2 Pages: 114-9

    • DOI

      10.1016/j.neulet.2012.10.032

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lipopolysaccharide-activated microglia lower P-glycoprotein function in brain microvascular endothelial cells.2012

    • Author(s)
      Matsumoto J, Dohgu S, Takata F, Nishioku T, Sumi N, Machida T, Takahashi H, Yamauchi A, Kataoka Y.
    • Journal Title

      Neurosci Lett.

      Volume: 524(1) Issue: 1 Pages: 45-8

    • DOI

      10.1016/j.neulet.2012.07.004

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-α, releasing matrix metalloproteinase-9 and migrating in vitro2011

    • Author(s)
      Takata F, Dohgu S, Matsumoto J, Takahashi H, Machida T, Wakigawa T, Harada E, Miyaji H, Koga M, Nishioku T, Yamauchi A, Kataoka Y.
    • Journal Title

      J Neuroinflammation.

      Volume: 8 Issue: 1 Pages: 106-106

    • DOI

      10.1186/1742-2094-8-106

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] A role for hypothalamic AMP-activated protein kinase in the mediation of hyperphagia and weight gain induced by chronic treatment with olanzapine in female rats.2011

    • Author(s)
      Sejima E, Yamauchi A, Nishioku T, Koga M, Nakagama K, Dohgu S, Futagami K, Kataoka Y
    • Journal Title

      Cell Mol Neurobiol.

      Volume: 31(7) Issue: 7 Pages: 985-9

    • DOI

      10.1007/s10571-011-9663-8

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potential role for S100A4 in the disruption of the blood-brain barrier incollagen-induced arthritic mice, an animal model of rheumatoid arthritis2011

    • Author(s)
      Nishioku T, Furusho K, Tomita A, Ohishi H, Dohgu S, Shuto H, Yamauchi A, Kataoka Y
    • Journal Title

      Neuroscience.

      Volume: 189 Pages: 286-92

    • DOI

      10.1016/j.neuroscience.2011.05.044

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of the cellular prion protein in the migration of brain microvascular e ndothelial cells2011

    • Author(s)
      Watanabe T, Yasutaka Y, Nishioku T, Ku sakabe S, Futagami K, Yamauchi A, Kata oka Y
    • Journal Title

      Neurosci Lett.

      Volume: 496(2) Issue: 2 Pages: 121-4

    • DOI

      10.1016/j.neulet.2011.03.096

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Partial hepatectomy aggravates cyclosporin A-induced neurotoxicity by lowering the function of the blood-brain barrier in mice.2011

    • Author(s)
      Yamauchi A, Dohgu S, Takata F, Watanabe T, Nishioku T, Matsumoto J, Ohkubo Y, Shuto H, Kataoka Y.
    • Journal Title

      Life Sci.

      Volume: 88(11-12) Issue: 11-12 Pages: 529-34

    • DOI

      10.1016/j.lfs.2011.01.012

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autocrine and paracrine up-regulation of blood-brain barrier function by plasminogen activator inhibitor-1.2011

    • Author(s)
      Dohgu S, Takata F, Matsumoto J, Oda M, Harada E, Watanabe T, Nishioku T, Shuto H, Yamauchi A, Kataoka Y.
    • Journal Title

      Microvascular research.

      Volume: 81(1) Issue: 1 Pages: 103-7

    • DOI

      10.1016/j.mvr.2010.10.004

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] BMP4による糖尿病併発動脈硬化巣の増悪とマクロファージの酸化LDL取り込み促進2013

    • Author(s)
      金岡祐輝、古賀允久、地下隆介、塚本安那、手島奈央、久保尚加、大城戸友麻、西奥剛、山内淳史、片岡泰文
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2013-03-22
    • Related Report
      2012 Final Research Report
  • [Presentation] 糖尿病病態下の動脈硬化巣におけるBMP4の役割2012

    • Author(s)
      古賀允久、金岡祐輝、地下隆介、西奥剛、山内淳史、片岡泰文
    • Organizer
      第65回日本薬理学会西南部会
    • Place of Presentation
      熊本
    • Year and Date
      2012-11-23
    • Related Report
      2012 Final Research Report
  • [Presentation] クプリゾン誘発脱髄動物モデルの大脳白質におけるCD147の発現変動2012

    • Author(s)
      津曲康輔、西奥剛、寺澤真理子、片岡泰文
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2012
    • Place of Presentation
      神戸
    • Year and Date
      2012-09-01
    • Related Report
      2012 Final Research Report
  • [Presentation] S100A4 is a causative factor for disruption of the blood-brain barrier in collagen-induced arthritic mice2012

    • Author(s)
      西奥剛 、山内淳史、片岡泰文
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      京都
    • Year and Date
      2012-03-14
    • Related Report
      2012 Final Research Report
  • [Presentation] S100A4 is a causative factor for disruption of the blood-brain barrier in collagen-induced arthritic mice2012

    • Author(s)
      Tsuyoshi Nishioku, Atsushi Yamauchi, and Yasufumi Kataoka
    • Organizer
      第85回日本薬理学会年会
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2011 Research-status Report
  • [Presentation] コラーゲン誘導関節炎マウスの滑膜におけるCyclophilinAとCD147の発現増加とその局在2011

    • Author(s)
      寺澤真理子、西奥剛、三浦哲平、津曲康輔、山内淳史、片岡泰文
    • Organizer
      第64回日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Year and Date
      2011-11-20
    • Related Report
      2012 Final Research Report
  • [Presentation] 関節リウマチの炎症性細胞浸潤機構におけるシクロフィリンAの役割2011

    • Author(s)
      大石裕晃、西奥剛、片岡泰文
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2011
    • Place of Presentation
      東京
    • Year and Date
      2011-08-31
    • Related Report
      2012 Final Research Report
  • [Presentation] 関節リウマチの炎症性細胞浸潤機構におけるシクロフィリンAの役割2011

    • Author(s)
      大石裕晃、西奥剛、片岡泰文
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2011
    • Place of Presentation
      北里大学薬学部白金キャンパス(東京)
    • Related Report
      2011 Research-status Report
  • [Presentation] コラーゲン誘導関節炎マウスの滑膜におけるCyclophilin AとCD147の発現増加とその局在2011

    • Author(s)
      寺澤真理子、西奥剛、三浦哲平、津曲康輔、山内淳史、片岡泰文
    • Organizer
      第64回日本薬理学会西南部会
    • Place of Presentation
      KKRホテル博多(福岡)
    • Related Report
      2011 Research-status Report
  • [Presentation] BMP4による糖尿病併発動脈硬化巣の増悪とマクロファージの酸化LDL取り込み促進

    • Author(s)
      金岡祐輝、古賀允久、地下隆介、塚本安那、手島奈央、久保尚加、大城戸友麻、西奥剛、山内淳史、片岡泰文
    • Organizer
      第86回日本薬理学会年会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 糖尿病病態下の動脈硬化巣におけるBMP4の役割

    • Author(s)
      古賀允久、金岡祐輝、地下隆介、西奥剛、山内淳史、片岡泰文
    • Organizer
      第65回日本薬理学会西南部会
    • Place of Presentation
      熊本大学薬学部(熊本)
    • Related Report
      2012 Annual Research Report
  • [Presentation] クプリゾン誘発脱髄モデル動物の大脳白質におけるCD147の発現変動

    • Author(s)
      津曲康輔、西奥剛、寺澤真理子、片岡泰文
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2012
    • Place of Presentation
      神戸学院大学(神戸)
    • Related Report
      2012 Annual Research Report

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

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