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HMG1 protein and its receptor : their distribution and clinical significance

Research Project

Project/Area Number 13470108
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

OZAKI Shoichi  St. Marianna Univ Sch Med Professor, 医学部, 教授 (00231233)

Co-Investigator(Kenkyū-buntansha) KOIKE Kaoru  Tohoku Univ Grad Sch Med Assoc Professor, 医学研究科, 助教授 (10267164)
YOSHIDA Michiteru  Science Univ Tokyo Professor, 基礎工学部, 教授 (20005648)
YAMADA Hidehiro  St. Marianna Univ Sch Med Assoc Professor, 医学部, 助教授 (00174730)
OHYA Kazuhiko  St. Marianna Univ Med Biology Laboratory Chief Investigator, 伊那研究所応用技術部, 主任研究員
村上 雅朗  京都大学, 医学研究科, 助手 (90301738)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2001: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsHMG1 / receptor / anti-HMG antibody / Shock / autoimmune disease / ELISA / epitope / RAGE
Research Abstract

We isolated high mobility group (HMG) nonhisitone chromosomal proteins 1 and 2 (HMG1/HMG2) as target antigens of anti-neutrophil cytoplasmic antibody (ANCA), and have been analyzing the roles of those autoantibodies as well as the autoantigens. We found the existence of anti-HMG1/HMG2 antibodies in 89% of patients with autoimmune hepatitis. These antibodies seemed to be useful clinical markers in the disease based on the highest prevalence and the correlation with disease activity. We also observed that HMG1 selectively enhanced the proliferation of cholangial cell lines in a dose-dependent manner.
We established an ELISA system for soluble HMG1 protein by using both polyclonal and monoclonal anti-HMG1/HMG2 antibody, which enabled us to test a serum HMG1 level as high as 10 micrograms/ml. We found that serum HMG1 reached a detectable level in fatal shock patients as long as we tested. We also established a novel fatal mouse model, in which 90% of the hepatic blood flow was blocked by a surgical procedure. All mice died 60 hr after the ligation, prior to which their serum HMG1 levels significantly increased. The survival rate increased by a simultaneous ip injection of monoclonal anti-HMG1 antibody. Taken together, these data indicates that HMG1 protein may play an important role in a certain fatal condition, and that the intervention of serum HMG1 levels may serve as a new strategy for such a critical state.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Okazaki T., Ozaki S., et al.: "Antigen-specific Th1 cell as direct effectors of Propionibacterium acnes-primed lipopolysaccharide-induced hepatic injury"Int. Immunol.. 13(5). 607-613 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akamizu T., Ozaki S., et al.: "Drug-induced neutropenia associated with anti-neutrophil cytoplasrmic antibodies (ANCA) : possible involvement of complement in granulocy tecytotoxicity"Clin Exp Immunol. 127. 92-98 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita Y., Ozaki S., et al.: "Leptin inhibits stress-induced apoptosis of T lymphocytes"Clin Exp Immunol 128. 128. 21-26 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fida S., Ozaki S.: "Autoantibodiesto the Transcriptional Factor SOX13 in Primary Biliary Cirrhosis Compared with Other Diseases"Journal of Autoimmunity. 19. 251-257 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka M., Ozaki S., et al.: "Potential preventive effects of follistatin-related protein/TSC-36 on joint destruction and antagonistic modulation of its autoantibodies in rheumatoid arthritis"Int. Immunol.. 15(1). 71-77 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 尾崎 承一: "治療学:薬物療法(免疫療法)。内科学(第8版)"朝倉書店(東京)杉本恒明, 小俣政男, 水野美邦編集. (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okazaki T., Ozaki S., Nagaoka T., Kozuki, M., Sumita S., Tanaka M., Osakada F., Kishimura M., Kakutani T. and Nakao K.: "Antigen-specific Th1 cell as direct effectors of Propionibacterium acnes-primed lipopolysaccharide-induced hepatic injury"Int. Immunol.. 13(5). 607-613 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akamizu T., Ozaki S., Hiratani H., Uesugi H., Sobagima J., Hataya Y., Kanamoto N., Saijo M., Hattori Y., Moriyama K., Ohmori K and Nakao K.: "Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA) : possible involvement of complement in granulocytecytotoxicity"Clin Exp Immunol. 127. 92-98 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujita Y., Murakami M., Ogawa Y., Masuzaki H., Tanaka M., Ozaki S., Nakao K and Mimori T.: "Leptin inhibits stress-induced apoptosis of T lymphocytes"Clin Exp Immunol. 128. 21-26 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fida S., Myers A. M., Whittingham S., Rowley j.M., Ozaki S., and Mackay R. I.: "Autoantibodies to the Transcriptional Factor SOX13 in Primary Biliary Cirrhosis Compared with Other Diseases"Journal of Autoimmunity. 19. 251-257 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka M., Ozaki S., Kawabata D., Kishimura M., Osakada F., Okubo M., Murakami M., Nakao K. and Mimori T.: "Potential preventive effects of follistatin-related protein / TSC-36 on joint destruction and antagonistic modulation of its autoantibodies in rheumatoid arthritis"Int. Immunol.. 15(1). 71-77 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okazaki T., Ozaki S., et al.: "Antigen-specific Th1 cell as direct effectors of Propionibacterium acnes-primed lipopolysaccharide-induced hepatic injury"Int. Immunol.. 13(5). 607-613 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akamizu T., Ozaki S., et al.: "Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA) : possible involvement of complement in granulocy tecytotoxicity"Clin Exp. Immunol. 127. 92-98 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujita Y., Ozaki S., et al.: "Leptin inhibits stress-induced apoptosis of T lymphocytes"Clin Exp Immunol 128:. 128. 21-26 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fida S., Ozaki S.: "Autoantibodiesto the Transcriptional Factor SOX13 in Primary Biliary Cirrhosis Compared with Other Diseases"Journal of Autoimmunity. 19. 251-257 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka M., Ozaki S., et al.: "Potential preventive effects of follistatin-related protein / TSC-36 on joint destruction and antagonistic modulation of its autoantibodies in rheumatoid arthritis"Int. Immunol.. 15(1). 71-77 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 尾崎承一: "治療学:薬物療法(免疫療法)。「内科学(第8版)」"朝倉書店(東京)杉本恒明, 小俣政男, 水野美邦編集. 2297 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ochiai K., Ozaki S., et al.: "Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone New Zealand Black mice"Int. Immunol.. 12・1. 1-8 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tanaka M., Ozaki S., et al.: "Cloning of novel soluble gp130 and detection of its neutralizing auto-antibodies in rheumatoid arthiritis"J. Clin. Invest.. 106・1. 137-144 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ma W., Ozaki S., et al.: "Detection of anti-neutrophil cytoplasmic antibodies in MRL/Mp-lpr/lpr mice and analysis of their target antigens"Autoimmunity. 32. 282-291 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yahata K., Ozaki S., et al.: "Molecular cloning and expression of a novel klotho-related protein"J. Mol. Med.. 78. 389-394 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okazaki T., Ozaki S., et al.: "Antigen-specific Th1 cell as direct effectors of Propionibacterium acnes-primed lipopolysaccharide-induced hepatic injury"Int. Immunol.. 13・5. 607-613 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 尾崎承一: "血管炎症候群の診断と病態把握:免疫血清学的検査。「血管炎」"朝倉書店(東京)長澤俊彦監修・橋本博史編集. (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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