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Identification of the transcriptional active region of the genome in autoimmune diseases.

Research Project

Project/Area Number 14570407
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionThe University of Tokyo

Principal Investigator

SAWADA Tetsuji  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (50235470)

Co-Investigator(Kenkyū-buntansha) INOUE Tesufumi  The University of-foreign Affairs, Health Care Center, Professor, 保健管理センター, 教授 (30092141)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordssuppression PCR / DNA methylation / Nuclear factor kappaB / 自己免疫疾患 / メチル化 / 転写活性化領域
Research Abstract

Human endogenous retrovirus (HERV) sequences are dispersed throughout the genome, which are thus considered to be a useful genetic marker for genome research. HERVs may participate in the pathogenesis of autoimmunity, via the formation of immune complexes after translation, or activation of the surrounding genes via their promoter /enhancer activity. The demethylation of cytosine at the CpG islands is associated with transcriptional activity In this study, the profile of CAN methylation around the hhh s were examined by suppression ppp. Adapter primer was added to the genomic ddd, which was degested with methylation-sensitive restriction enzyme(HpaII). Suppression ppp was subsequently performed tor ampligy the HpaII fragments containing hhh sequences, using the primer for adapter sequence, and the fluorescence-labeled primer comon to the various hhh sss (U5 and U3 region ). S control, metylation-insensitve restriction enzyme(MspI) was used, and the length of fragments was analyzed by a … More utomatic sssr. The profile of suppression ppp using HpaII fragments as template was different between neutrophils and and lymph nodes. In contrast the profile using MspI fragments as template was identical. Therefore, it is considered that the different profile of suppression ppp may result from the methylation-status (epigenetic) defference among the tissues. As to rheumatoid arthritis (RA),PADI4 was demonstrated to be in RA, although the relevance of its methylation was unknown. On the other hand, NF-kB inhibitors was also investigated. Among the chemicals, designed via computere-assisted drug design, the compound was selected as most effective inhibitor of transcriptional NF-kB activity, the proliferation and the production of proinflammatory cytokines from synovial cell lines. The compund was effective in mouse collagen artrits model at a dosage of 1-3mg/kg, shich is promising as novel anti-rheumatic therapy, although further study investigating its safety profile is necessary. The effect of this compund on the methylation profile around perform for the analysis of the entire profile of methylation, it would be useful for the investigation of epigenetic factor (methylation status) of genome DNA in various autoimmune diseases. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Suzuki K, Sawada T et al.: "High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis."Scandinavian Journal of Rheumatology. 32・4. 197-204 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki A et al.: "Functional haplotypes of PADI4,encoding citrullinating enzyme peptidylarginine deiminase 4,are associated with rheumatoid arthritis."Nature Genetics. 34・4. 395-402 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki K, Sawada T et al.: "High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis"Scandinavian Journal ofRheumatology. 32(4). 197-204 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki A et al.: "functional haplytypes of PADI4,encoding citrullinating enzyme peptidylarginine deiminase4, are associated with rheumatoid arthritis."Nature Genetics. 32(4). 395-402 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki K, Sawada T et al.: "High diagnostic performance of ELISA detection of antibodies to citrullinated antigens in rheumatoid arthritis."Scandinavian Journal of Rheumatology. 32・4. 197-204 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki A et al.: "Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis."Nature Genetics. 34・4. 395-402 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 沢田哲治: "関節炎重症例の薬物治療の実際"Medical Practice. 19巻7号. 1189-1193 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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