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Analysis of the inhibitory mechanisms of IFN gamma induced gene expression by hypoxia

Research Project

Project/Area Number 22791797
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionMeikai University

Principal Investigator

HIROI Miki  明海大学, 歯学部, 助教 (30419717)

Project Period (FY) 2010-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsシグナル伝達 / 低酸素 / インターフェロン / ケモカイン / 遺伝子制御
Research Abstract

We have previously shown that hypoxia down-regulated the IFN-induced expression of chemokine CXCL9 and CXCL10 genes in human tumor cell lines. We have explored the mechanisms by which hypoxia down-regulates the IFN-induced gene expressions and found that although HIF-1 was not involved in the transcriptional repression of the IFN-induced genes, recruitments of Pol II, coactivator SRC-1 were inhibited under the hypoxia. In this study, we investigated potential involvements of HIF-2, histone methylation at the promoter region of the CXCL9 genes, and mediator complex that participates in the recruitment of Pol II for the hypoxia-mediated transcriptional repression. Over expression of an active form of HIF-2 in HEK293 cells inhibited the CXCL9 promoter activity, suggesting that HIF-2 negatively regulates CXCL9 expression. Real-time RT-PCR analysis showed that constitutive expressions of mRNAs for methyltransferase and members of mediator complex were observed in HSC-2 cells.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (2 results)

All 2010

All Presentation (2 results)

  • [Presentation] 低酸素はIFNγ誘導性ケモカインCXCL9/Mig,CXCL10/IP-10 の発現を抑制する2010

    • Author(s)
      廣井美紀, 大森喜弘
    • Organizer
      第52回歯科基礎医学会学術大会・総会
    • Place of Presentation
      東京都
    • Year and Date
      2010-09-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 低酸素はIFNγ誘導性ケモカインCXCL9/Mig、CXCL10/IP-10の発現を抑制する2010

    • Author(s)
      廣井美紀、大森喜弘
    • Organizer
      第52回歯科基礎医学会学術大会・総会
    • Place of Presentation
      タワーホール船堀(東京都)
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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