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Mechanisms of Sequence-Dependent Activation in CpG DNA-Stimulated Human Cells

Research Project

Project/Area Number 16590355
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionUniversity of Fukui

Principal Investigator

IHO Sumiko  University of Fukui, Pathological Sciences, Assistant Professor, 医学部, 助手 (80151653)

Co-Investigator(Kenkyū-buntansha) TAKATSUKA Hisakazu  University of Fukui, International Social and Health Sciences, Assistant Professor, 医学部, 助手 (40242490)
IWASAKI Hiromichi  University of Fukui, General Medicine, Associate Professor, 医学部, 助教授 (10242588)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsCpG DNA / IFN-α / IRF-7 / pDC / NF-κB / p38 MAPK / CXCL10 / CCL3 / IFN / IgE / 形質細胞様樹状細胞 / INF-α / IRF / IP-10
Research Abstract

The immunostimulatory activities of CpG DNA differ with their own sequences. Using polyG-flanked palindromic CpG DNA (unmodified), we examined the mechanisms through which CpG DNA activates plasmacytoid dendritic cells (pDC) in humans.
In pDC, NF-κB family proteins p65 and p50 were constitutively activated. pDC also constitutively expressed IRF-7 and CCL3, and the expression of these genes seemed to be regulated by NF-κB. CpG DNA enhanced the NF-κB p65/p50 activity, which collaborated with p38 MAPK downstream of TLR9 to up-regulate the expressions of IRF-7, CXCL10, and CCL3 in a manner independent of type I IFN signaling. Following the simulation with CpG DNA, IRF-7, both constitutively and newly expressed, moved to the nuclei in a manner independent of NF-κB/p38 MAPK to transcribe the gene for IFN-α. IFN-α, secreted once, returned to pDC and upregulated the expression of IRF-7 independently of NF-κB/p38 MAPK. CpG DNA suppressed IgE production via the activation of pDC.
These findings suggest that (1) there are two pathways in CpG DNA-stimulated human pDC : one dependent on NF-κB and the other independent of NF-κB. The former induces IRF-7, CXCL10, and CCL3, whereas the latter is involved in the activation of IRF-7. (2) IRF-7 induced independently of type I IFN signaling appears to be important for the expression of IFN-α, as the inhibition of NF-κB pathway abrogated the expression of IFN-α. (3) Activation of pDC by CpG DNA would be a promising strategy for inhibiting allergy, as CpG DNA-stimulated pDC suppressed IgE production.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (16 results)

All 2006 2005 2004

All Journal Article (16 results)

  • [Journal Article] 福井大学重点研究「競争的配分経費」形質細胞様樹状細胞におけるInterferon Regulatory Factor-7活性化機構の解析2006

    • Author(s)
      伊保澄子
    • Journal Title

      福井大学重点研究成果集2005 (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 福井大学重点研究「基礎的・萌芽的研究」免疫誘導活性を持つ新規非定型配列オリゴヌクレオチドの実用化への基礎的研究2006

    • Author(s)
      松木孝澄
    • Journal Title

      福井大学重点研究成果集2005 (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activation Mechanism of IRF-7 in plasmacytoid dendritic cells (in Japanese)2006

    • Author(s)
      Sumiko Iho
    • Journal Title

      Proceedings for priority research of Fukui University (Fukui-daigaku Jyutenn-kennkyu Seika-shu) (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Newly developed-atypical oligoDNA which possesses immunostimulatory activity - Basic study for clinical application (in Japanese).2006

    • Author(s)
      Takasumi Matsuki
    • Journal Title

      Proceedings for priority research of Fukui University (Fukui-daigaku Jyutenn-kennkyu Seika-shu) (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 喫煙による白血球増加とサイトカイン2005

    • Author(s)
      伊保 澄子
    • Journal Title

      Life Support and Anesthesia 12

      Pages: 438-443

    • Related Report
      2005 Annual Research Report
  • [Journal Article] CpG DNAによるplasmacytoid樹状細胞の活性化2004

    • Author(s)
      高氏留美子
    • Journal Title

      臨床免疫 41・1

      Pages: 107-112

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] CpG DNAによるplasmacytoid樹状細胞のインターフェロン・α産生におけるシグナル伝達2004

    • Author(s)
      高氏留美子
    • Journal Title

      臨床免疫 42・1

      Pages: 127-133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] PolyG-flanked palindromic CpG DNA activates STAT1 and NF-κB through the p38 MAPK pathway to induce autocrine IFN-α/β-independent production of IFN-α, IP-10, and MIP-1α in human plasmacytoid dendritic cells.2004

    • Author(s)
      Osawa, Y.
    • Journal Title

      J. Endotoxin Res. 10・5

      Pages: 350-351

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impaired hepatic granuloma formation with normal host defense in Myd88-deficient mice.2004

    • Author(s)
      Takatsuka, H.
    • Journal Title

      J. Endotoxin Res. 10・5

      Pages: 363-363

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 「Lecture」 Activation of plasmacytoid dendritic cells by CPG DNA (in Japanese).2004

    • Author(s)
      Rumiko Takauji
    • Journal Title

      Clin.Immunol. 41

      Pages: 107-112

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 「Lecture」 Mechanism of CpG DNA-induced IFN-α production in pDC (in Japanese).2004

    • Author(s)
      Rumiko Takauji
    • Journal Title

      Clin.Immunol. 42

      Pages: 127-133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] PolyG-flanked palindromic CpG DNA activates STAT1 and NF-κB through the p38 MAPK pathway to induce autocrine IFN-α/β-independent production of IFN-α, P-10, and MIP-1α in human plasmacytoid dendritic cells.2004

    • Author(s)
      Osawa, Y.
    • Journal Title

      J.Endotoxin Res. 10

      Pages: 350-351

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impaired hepatic granuloma formation with normal host defense in Myd88 -deficient mice.2004

    • Author(s)
      Takatsuka, H.
    • Journal Title

      J.Endotoxin Res. 10

      Pages: 363-363

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CpG DNAによるplasmacytoid樹状細胞のインターフェロン-α産生におけるシグナル伝達2004

    • Author(s)
      高氏留美子
    • Journal Title

      臨床免疫 42・1

      Pages: 127-133

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PolyG-flanked palindromic CpG DNA activates STAT1 and NF-κB through the p38 MAPK pathway to induce autocrine IFN-α/β-independent production of IFN-α, IP-10, and MIP-1α in human plasmacytoid dendritic cells.2004

    • Author(s)
      Osawa, Y.
    • Journal Title

      J Endotoxin Res 10・5

      Pages: 350-350

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Impaired hepatic granuloma formation with normal host defense in Myd88-deficient mice.2004

    • Author(s)
      Takatsuka, H.
    • Journal Title

      J Endotoxin Res 10・5

      Pages: 363-363

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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