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Identification of a novel role for innate immune sensor NLRP

Research Project

Project/Area Number 23590327
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKanazawa University

Principal Investigator

KINOSHITA TAKESHI  金沢大学, がん進展制御研究所, 助教 (20311681)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords細胞内シグナル伝達 / がん / シグナル伝達 / 免疫
Research Abstract

The nucleotide-binding oligomerization domain-like receptors (NLR ) family member NLRP3 is a central regulator of innate immunity. We recently found that NLRP3 mediates NF-kappaB activation and cytokine transcription in human monocytic cell line THP-1 following microbial infection. In this study, we examined the effect of NLRP3 knockdown on cytokine induction following sterile stimulation to clarify the physiological relevance of this function. NLRP3 knockdown reduced cytokine induction in THP-1 and human monocytes following sterile stimulation. Next, we examined the role of NLRP3 in tumor cell lines. NLRP3 knockdown reduced the constitutive expression of IL-1beta in these tumor cell lines. Interestingly, the expression of TGF-beta, IL-6, and matrix metalloproteinase were reduced in knockdown cells. These data suggest that NLRP3 not only mediates cytokine transcription for innate immunity but also contributes tumor progression through the induction of tumor-related gene expression.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (8 results)

All 2012 2011 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated necrosis independently of its catalytic activity2011

    • Author(s)
      Motani K., Kushiyama H., Imamura R., Kinoshita, T., Nishiuchi T., Suda T.
    • Journal Title

      J. Biol. Chem

      Volume: 286 Pages: 33963-33972

    • NAID

      120003479727

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Caspase-1 protein induces apoptosis-associated speck-like protein containing a caspase recruit ment domain(ASC)-mediated necrosis ind ependently of its catalytic activity2011

    • Author(s)
      Motani, K., Kushiyama, H., Imamura, R., et. al.
    • Journal Title

      J. Biol. Chem

      Volume: 286 Issue: 39 Pages: 33963-33972

    • DOI

      10.1074/jbc.m111.286823

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] The role of NLRP3 in the induction of cytokine gene expression in tumor cells2012

    • Author(s)
      木下健, 今村龍, 須田貴司
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-12
    • Related Report
      2013 Final Research Report
  • [Presentation] NLRP3 mediates NF-B activation and cytokine induction in microbially induced and sterile inflammation2011

    • Author(s)
      木下健, 今村龍, 須田貴司
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-14
    • Related Report
      2013 Final Research Report
  • [Presentation] The role for NLRP3 in the induction of cytokine gene expression in tumor cells

    • Author(s)
      akeshi Kinoshita, Ryu Imamura, Takashi Suda
    • Organizer
      第35回に本分子生物学会年会
    • Place of Presentation
      マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] NLRP3 mediates NF-κB activation and cytokine induction in microbially induced and sterile inflammation

    • Author(s)
      Takeshi Kinoshita, Ryu Imamura, Takashi Suda
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.kanazawa-u.ac.jp/~ganken/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://web.kanazawa-u.ac.jp/~cdmtd/index.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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