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Analysis of pathophysiology and novel therapeutic approach for rheumatic diseases by arthritis-regulated proteins

Research Project

Project/Area Number 18390290
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKyoto University

Principal Investigator

MIMORI Tsuneyo  Kyoto University, 大学院医学研究科医学研究科・内科学講座臨床免疫学, 教授 (10157589)

Co-Investigator(Kenkyū-buntansha) 藤井 隆夫  京都大学, 医学研究科, 講師 (70255462)
臼井 崇  京都大学, 医学研究科, 准教授 (90362483)
田中 真生  金沢医科大学, 医学部, 講師 (10332719)
Co-Investigator(Renkei-kenkyūsha) FUJII Takao  京都大学, 大学院・医学研究科, 講師 (70255462)
USUI Takashi  京都大学, 大学院・医学研究科, 准教授 (90362483)
TANAKA Masao  金沢医科大学, 医学部, 講師 (10332719)
Research Collaborator ITO Yoshinaga  京都大学, 大学院・医学研究科, 大学院生
HASHIMOTO Mikiko  京都大学, 大学院・医学研究科, 大学院生
MURAKLAMI Kosaku  京都大学, 大学院・医学研究科, 大学院生
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,100,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2007: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2006: ¥6,400,000 (Direct Cost: ¥6,400,000)
Keywords関節リウマチ / 自己抗体 / カルパイン / カルパスタチン / FRP / コラーゲン誘発関節炎 / フォリスタチン関連蛋白 / IL-6 / CD4陽性T細胞 / ホリスタチン関連蛋白 / Th1 / Th2バランス
Research Abstract

本研究は、以前に見出した関節リウマチ(RA)の新たな自己抗体である抗カルパスタチン抗体と抗FRP抗体の対応抗原がいずれも関節炎抑制作用を示したことから、これらの自己抗体がRAの発症と増悪に関与する病原性自己抗体ではないかと考え、これら自己抗原および自己抗体の制御によって関節炎を治療できる可能性を追求した。カルパイン(カルシウム依存性中性プロテアーゼ)の特異的インヒビターであるカルパスタチンは線維芽細胞のIL-6産生を抑制するだけでなく、T細胞分化にも影響することが判明した。関節炎モデルにおいてはカルパスタチンは炎症を抑制しカルパインは増強した。フォリスタチン関連蛋白(FRP)はヒトとマウスで炎症の制御に関して異なる働きを有する可能性が示唆され、マウス関節炎に対してヒトFRPは抑制したが逆にマウスFRPは増強した。これらの炎症制御蛋白の解析により関節炎病態の理解と新たな治療法開発の可能性が示唆される。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (34 results)

All 2009 2008 2007 2006 Other

All Journal Article (29 results) (of which Peer Reviewed: 22 results) Presentation (4 results) Book (1 results)

  • [Journal Article] Autoimmune autonomic ganglionopathy with Sjogren's syndrome : Significance of ganglionic acetylcholine receptor antibody and therapeutic approach2009

    • Author(s)
      Kondo T, Inoue H, Usui T, Mimori T, Tomimoto H, Vernino S, Takahashi R
    • Journal Title

      Auton Neurosci. Auton Neurosci 146(1-2)

      Pages: 33-5

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] y δT cells are predominant source of IL-17 in the affected joints of collagen-induced arthritis, but not in rheumatoid arthritis2009

    • Author(s)
      Ito Y, Usui T, Fujii T, Mimori T, et al
    • Journal Title

      Arthritis Rheum (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired TCR signaling through dysfunction of lipid rafts in sphingomyelin synthase 1 (SMS1)-knockdown T cells2008

    • Author(s)
      Jin ZX, Huang CR, Dong L, Goda S, Kawanami T, Sawaki T, Sakai T, Tong XP, Masaki Y, Fukushima T, Tanaka M, Mimori T, Tojo H, Bloom ET, Okazaki T, Umehara H
    • Journal Title

      Int Immunol 20(11)

      Pages: 1427-37

    • NAID

      10024357803

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aseptic meningitis in mixed connective tissue disease : cytokine and anti-U1RNP antibodies in cerebrospinal fluids from two different cases2008

    • Author(s)
      Fujita Y, Fujii T, Nakashima R, Tanaka M, Mimori T
    • Journal Title

      Mod Rheumatol 18(2)

      Pages: 84-8

    • NAID

      10024150446

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aseptic meningitis in mixed connective tissue disease : cytokine and anti-U1RNP antibodies in cerebrospinal fluids from two different cases2008

    • Author(s)
      Fujita Y, Fujita Y, Nakashima R, Tanaka M, Mitnori T
    • Journal Title

      Mod Rheumatol 18(2)

      Pages: 184-188

    • NAID

      10024150446

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired TCR signaling through dysfimction of liqid rafts in sphingomyelin synthase l(SMSl)-knockdown T cells2008

    • Author(s)
      Jin ZX, Tanaka M, Mimori T, et al
    • Journal Title

      International Immunology 20(11)

      Pages: 1427-1437

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aseptic meningitis in mixed connective tissue disease: cytokine and anti-UIRNP antibodies in cerebrospinal fluids from two different cases.2008

    • Author(s)
      Fujita Y, Fujii T, Nakashima R, Tanaka M, Mimori T
    • Journal Title

      Mod Rheumatol 18(2)

      Pages: 184-188

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of mizoribine for the treatment of Sjogren's syndrome : a multicenter open-label clinical trial2007

    • Author(s)
      Nakayamada S, Saito K, Umehara H, Ogawa N, Sumida T, Ito S, Minota S, Nara H, Kondo H, Okada J, Mimori T, Yoshifuji H, Sano H, Hashimoto N, Sugai S, Tanaka Y
    • Journal Title

      Mod Rheumatol 17(6)

      Pages: 464-9

    • NAID

      10020178053

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autoantibodies in idiopathic inflammatory myopathy : an update on clinical and pathophysiological significance2007

    • Author(s)
      Mimori T, Imura Y, Nakashima R, Yoshifuji H
    • Journal Title

      Curr Opin Rheumatol 19(6)

      Pages: 523-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Incidence of pulmonary hypertension and its clinical relevance in patients with interstitial pneumonias : comparison between idiopathic and collagen vascular disease associated interstitial pneumonias2007

    • Author(s)
      Handa T, Nagai S, Miki S, Ueda S, Yukawa N, Fushimi Y, Ito Y, Ohta K, Mimori T, Mishima M, Izumi T
    • Journal Title

      Intern Med 46(12)

      Pages: 831-7

    • NAID

      130000076693

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Severe subcutaneous generalized edema in a patient with dermatomyositis2007

    • Author(s)
      Ito Y, Kawabata D, Yukawa N, Yoshifuji H, Usui T, Tanaka M, Fujii T, Mimori T
    • Journal Title

      Mod Rheumatol 17(2)

      Pages: 171-3

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of a patient with refractory adult Still's disease by tacrolimus2007

    • Author(s)
      Murakami K, Fujii T, Yukawa N, Yoshifuji H, Kawabata D, Tanaka M, Usui T, Mimori T
    • Journal Title

      Mod Rheumatol 17(2)

      Pages: 167-70

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase2007

    • Author(s)
      Hirakata M, Suwa A, Takada T, Sato S, Nagai S, Genth E, Song YW, Mimori T, Targoff IN
    • Journal Title

      Arthritis Rheum 56(4)

      Pages: 1295-303

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of primary Sjogren's syndrome with chronic natural killer lymphocytosis by high-dose prednisolone and indomethacin farnesil2007

    • Author(s)
      Fujita Y, Fujii T, Takeda N, Tanaka M, Mimori T
    • Journal Title

      Intern Med 46(5)

      Pages: 251-4

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of rituximab(anti-CD20)for refractory systemic lupus erythematosus involving the central nervous system2007

    • Author(s)
      Tokunaga M, Saito K, Kawabata D, Imura Y, Fujii T, Nakayamada S, Tsujimura S, Nawata M, Iwata S, Azuma T, Mimori T, Tanaka Y
    • Journal Title

      Ann Rheum Dis 66(4)

      Pages: 470-5

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autoantibodies in idiopathic inflammatory myopathy: an update on clinical and pathophysiological significance.2007

    • Author(s)
      Mimori T, Imura Y, Nakashima R, Yoshifuji H
    • Journal Title

      Curr Opin Rheumatol 19(6)

      Pages: 523-528

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of rituximab(anti-CD20)for refractory systemic lupus erythematosus involving the central nervous system.2007

    • Author(s)
      Tokunaga M, Mimori T, et. al.
    • Journal Title

      Ann Rheum Dis 66(4)

      Pages: 470-475

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of primary Sjogren's syndrome with chronic natural killer lymphocytosis by high-dose prednisolone and indomethacin farnesil.2007

    • Author(s)
      Fujita Y, Fujii T, Takeda N, TanakaM, Mimori T
    • Journal Title

      Intern Med 46(5)

      Pages: 251-254

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase.2007

    • Author(s)
      Hirakata M, Mimori T, et. al.
    • Journal Title

      Arthritis Rheum 56(4)

      Pages: 1295-1303

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of anti-CCP antibody in diagnosis of collagen diseases2007

    • Author(s)
      三森経世
    • Journal Title

      日本内科学会雑誌 96(10)

      Pages: 2132-2137

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system.2007

    • Author(s)
      Tokunaga M, Mimori T, et al.
    • Journal Title

      Ann Rheum Dis 66(4)

      Pages: 470-475

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase.2007

    • Author(s)
      Hirakata M, Mimori T, et al.
    • Journal Title

      Arthritis Rheum 56(4)

      Pages: 1295-1303

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Anti-aminoacyl-tRNA synthetase antibodies in clinical course prediction of interstitial lung disease complicated with idiopathic inflammatory myopathies2006

    • Author(s)
      Yoshifuji H, Fujii T, Kobayashi S, Imura Y, Fujita Y, Kawabata D, Usui T, Tanaka M, Nagai S, Umehara H, Mimori T
    • Journal Title

      Autoimmunity 39(3)

      Pages: 233-241

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-p97/VCP antibodies : an autoantibody marker for a subset of primary biliary cirrhosis patients with milder disease2006

    • Author(s)
      Miyachi K, Hosaka H, Nakamura N, Miyakawa H, Mimori T, Shibata M, Matsushima S, Chinoh H, Horigome T, Hankins RW, Zhang M, Fritzler MJ
    • Journal Title

      Scand J Immunol 63(5)

      Pages: 376-382

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-aminoacyl-tRNA synthetase antibodies in clinical course prediction of interstitial lung disease complicated with idiopathic2006

    • Author(s)
      Yoshifuji H, Mimori T, et al.
    • Journal Title

      Autoimmunity 39(3)

      Pages: 233-241

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Anti-p97/VCP antibodies : an autoantibody marker for a subset of primary biliary cirrhosis patients with milder disease?2006

    • Author(s)
      Miyachi K, Mimori T, et al.
    • Journal Title

      Scand J Immunol 63(5)

      Pages: 376-382

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Antisynthetase syndrome associated with sarcoidosis.2006

    • Author(s)
      Asanuma Y, Mimori T, et al.
    • Journal Title

      Intern Med 45(18)

      Pages: 1065-1068

    • NAID

      130000076442

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 関節リウマチと抗シトルリン化蛋白抗体.2006

    • Author(s)
      三森経世
    • Journal Title

      BIO Clinica 21(10)

      Pages: 901-907

    • Related Report
      2006 Annual Research Report
  • [Journal Article] γδT Cells are the predominant source of IL-17 in the affected joints of collagen-induced arthritis, but not in rheumatoid arthritis

    • Author(s)
      Ito Y, Usui T, Kobayashi S, Iguchi-Hashimoto M, Ito H, Yoshitomi H, Nakamura T, Shimizu M, Kawabata D, Yukawa N, Hashimoto M, Sakaguchi N, Sakaguchi S, Yoshifuji H, Nojima T, Ohmura K, Fujii T, Mimori T
    • Journal Title

      Arthritis Rheum (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] Follistatin-related protein (FRP)/FSTL1 is one ofthe regulators of IL-6 production in fibroblast-derived cell lines2008

    • Author(s)
      Murakami K, Tanaka M, Usui T, Mimori T
    • Organizer
      第38回日本免疫学会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] Ameriolation of experimental myositis by a calpain-inhibitory compound.2007

    • Author(s)
      Yoshifuji H, Usui H, Itoh Y, Hashimoto M, Mimori T
    • Organizer
      The 71th Annual Meeting of the American College of Rheumatology
    • Place of Presentation
      Boston
    • Related Report
      2007 Annual Research Report
  • [Presentation] 疾患特異的な免疫制御法の可能性.2007

    • Author(s)
      臼井 崇、藤井隆夫、三森経世, ほか
    • Organizer
      第51回日本リウマチ学会総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] ホリスタチン関連蛋白(FRP)/FSTL1を投与した関節炎マウス関節組織におけるcDNAアレイ解析2007

    • Author(s)
      田中 真生、藤井 隆夫、三森経世, ほか
    • Organizer
      第51回日本リウマチ学会総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Book] Autoantibodies and Autoimmunity2006

    • Author(s)
      Pollard KM, Mimori T, et al.
    • Total Pages
      608
    • Publisher
      Wiley-VCH (Weinheim, Germany)
    • Related Report
      2006 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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