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Analysis of pathogenesis of Ulcerative colitis utilizing HLA-DPw9 transgenic mice

Research Project

Project/Area Number 09670561
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

SAKAMAKI Sumio  Sapporo Medical University, School of Internal Medicine, Medicine, 4th Department of Assistant Professor, 医学部, 講師 (00196081)

Co-Investigator(Kenkyū-buntansha) TAKAYAMA Tetsuji  Sapporo Medical University, School of Medicine, 4th Department of Internal Medic, 医学部, 助手 (10284994)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsHLA-DPAw9 / ADCC / Tropomyosin / ELISA / Peptide / Transgenic mice
Research Abstract

Background & Aims : Recent studies suggest that tropomyosin (TM) may act as a putative autoantigen in ulcerative colitis (UC). Recently, we identified by computer homology analysis a specific peptide (HIAEDADRK) in human TM that can bind to HLA-DPw9. This specific HLA molecule was also reported to be associated with UC patients in Japan. The aim of this study was to investigate the role of HLA-DPw9 in pathogenesis of UC by checking antibody against this specific peptide associated with HLA-DPw9 and establishing a UC model using HLA-DPw9 transgenic mice. Methods : (1) Antibodies were measured by ELISA with a synthetic peptide in 20 healthy volunteers, 48 patients with UC, 26 with Crohn's disease (CD), 3 with primary sclerosing cholangitis (PSC), and 6 with primary biliary cirrhosis (PBC). The functional significance of antibodies was investigated by antibody dependent cell mediated cytotoxicity (ADCC) against DPw9 transfected L cells by standard 51Cr release assay. (2) To investigate wh … More ether HLA-DPw9 transgenic mice develop UC, they were treated with TAK 603 (T helper 1 specific inhibitor provided by TAKEDA Co. Ltd.).
Results : (1) OD values of sera from UC (1.50*0.47) and PSC (1.90*0.11) were significantly higher than those from healthy volunteers (0.62*0.24) (p<O.05), CD (0.73*0.35) (p<O.05) and PBC (0.45*0.12) (p<O.O5). The values in UC decreased with clinical improvement. The ADCC activity of UC sera correlated well to the antibody titer against this synthetic peptide.
(2) HLA-DPw9 transgenic mice did not develop UC by TAK 603.
Conclusions : In this study, we revealed that a specific epitope of TM was capable of humoral immune response in patients with UC and PSC.This may provide important biochemical information to explain the autoimmune mechanism in UC and PSC, and may help in the development of strategies for possible immune therapy such as antigen-based immunointervention utilizing this specific pepticte, For developing UC in HLA-DPw9 transgenic mice other agent triggering inflammation than TAK 603 will benecessary. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Hirayama Y,Sakamaki S,et al.: "Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura,aplastic anemia,and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells." Blood.92. 46-52 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Niitsu Y,Sakamaki S,et al.: "A proof of glutathione S-transferase-π-related multidrug resistance by transfer of antisense gene to cancer cells and sense gene to bone marrow stem cell." Chemico-Biological Interactions.111-112. 325-332 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takayama T,Sakamaki S,et al.: "Abberant crypt foci of the colon as precursors of adenomas and cancer." New Eng J Med.339. 1277-1284 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Naohito Yoshizaki, Sumio Sakamaki, Shuya Hayashi, Norihiro Takayanagi, Yoshiro Niitsu.: "Increased poprlation of Th2 like cells with a phenotype of CD45RO+CD62L+ in patients with Ulcerative colitis." Gastroenterol. 114. A1121 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sumio Sakamaki, Shinichi Katsuki, Tetsuji Takayama, Naohito Yoshizaki, Masao Ohi, Atsushi Nobuoka, Norihiro Takayanagi, Toshiro Niitsu.: "Increment of the number of aberrant crypt foci In Ulcerative colitis patients." Gastroenterol. 114. A1074 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirayama Y,Sakamaki S,et al.: "Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells." Blood.92. 46-52 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Niitsu Y,Sakamaki S,et al.: "A proof of glutathione S-transferase-π-related multidrug resistance by transfer of antisense gene to cancer cells and sense gene to bone marrow stem cell." Chemico-Biological Interactions.111-112. 325-332 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takayama T,Sakamaki S,et al.: "Abberant crypt foci of the colon as precursors of adenomas and cancer." New Eng J Med.339. 1277-1284 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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