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Characterization of MCP-1 Transcriptional regulation basic investigation of possible gene therapy for arthritis using animal model

Research Project

Project/Area Number 12670433
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionYokohama City University

Principal Investigator

ISHIGATSUBO Yoshiaki  Yokohama City Univ., Medicine, Professor, 医学部, 教授 (40137039)

Co-Investigator(Kenkyū-buntansha) UEDA Atsuhisa  Yokohama City Univ., Medicine, Assistant, 医学部, 助手 (60295483)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsMCP-1 / transcription / mRNA stability / adenovirus / B-lymphocytes / 単球遊走因子(MCP-1) / 慢性関節リウマチ / 転写制御
Research Abstract

We previously established that the nuclear factors Sp1 and NF-kB are critically involved in regulating human MCP-1 gene transcription. NF-kB is constitutively activated in B lymphocytes, raising the possibility that MCP-1 is also constitutively expressed by these cells. PCR analysis of resting peripheral blood B cells, however, detected no evidence of MCP-1 mRNA production. In contrast, human B cells incubated for 5 days with a combination of IL-10 plus anti-CD40, responded to LPS and TPA stimulation by significantly increasing MCP-1 mRNA levels. Under the same conditions, NF-kB was not up-regulated, suggesting that the increase in MCP-1 mRNA did not reflect increased rates of gene transcription. Additional studies to identify the mechanism underlying the accumulation of MCP-1 mRNA were performed using the human RPM1 8226 B cell line, which mirrored the response of peripheral blood B cells. LPS and TPA strongly up-regulated MCP-1 mRNA expression in RPM1 8226 cells. Of interest, this treatment did not alter the binding of NF-kB to the MCP-1 5'-flanking sequence, but did prolong the half-life of MCP-1 mRNA by up to 15-fold. These findings indicate that changes in MCP-1 mRNA expression are dependent on post-transcriptional regulation. Current efforts are directed towards investigating the control of MCP-1 expression in vivo. Towards that end, we constructed a recombinant adenovirus encoding expression cassete containing murine MCP-1. This adenovirus has been shown to efficiently infect target cells, which up-regulate expression of the exogenous MCP-1 present in the recombinant virus. Future studies will solve a role of MCP-1 on the pathogenesis of Rheumatoid arthritis.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Tanaka M: "Cell cycle dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1"J Biol Chem. 14. (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mori N: "Induction of monocyte Chemoattractant Protein 1 by Helicobacter pylori Involves NF-κB"Infection and Immunity. 69. (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka M: "Cell cycle dependent regulation of human aurora A transcription is mediated by periodic repression of E4TF1"J Biol Chem. 14. (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yawata M: "Nucleotide sequence analysis of the approximately 35-kb segment containing interferon-gamma-inducible mouse proteasome activator genes"Immunogenetics. 53. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto N: "Immune response induced by airway sensitization after influenza A virus infection depends on timing of antigen exposure in mice"J Virol. 75. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamaji S: "A novel integrin-linked kinase-binding protein, affixin, is involved in the early stage of cell-substrate interaction"J Cell Biol. 153. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuji T: "A case of psoas abscess in a patient with systemic sclerosis and rheumatoid arthritis"Mod Rheumatol. 11. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohno M: "Remitting fasciitis without eosinophilia : a new disease entity ? A case report"Rheumatology(Oxford). 40. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue S: "Transfer of heme oxygenase 1 cDNA by a replication-deficient adenovirus enhances interleukin 10 production from alveolar macrophages that attenuates lipopolysaccaride-induced acute lung injury in mice"Hum Gene Ther. 12. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hashiba T: "Adenovirus-medliated transfer of heme oxygenase-1 cDNA attenuates severe lunginjury induced by the influenza virus in mice"Gene Ther. 8. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hagiwara E: "Cigarette smoking depletes cells spontaneously secreting Th(1) cytokines in the human airway"Cytokine. 14. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeshita F: "Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated reguration of human IL-6 gene expression"Eur J Immunol. 30. (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki M: "Immune responses against replication-deficient adenovirus inhabit ovalbumin-specific allergic reactions in mice"Hum Gene Ther. 11. (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ihata A: "Severity of seropositive isolated Raynaud's phenomenon is associated with serological Drofile"J Rheumatol. 27. (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hagiwara E: "IL-12-encoding plasmid has a beneficial effect on spontaneous autoimmure disease in MRL/MP-lpr mice"Cytokine. 12. (2000)

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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