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The effect of intermedilysin on human bile duct cells

Research Project

Project/Area Number 18592003
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionThe University of Tokushima

Principal Investigator

HIROTA Katsuhiko  The University of Tokushima, Institute of Health Bioscience Graduate School, associate professor (60199130)

Co-Investigator(Kenkyū-buntansha) MIYAKE Yoichiro  The University of Tokushima, Institute of Health Bioscience Graduate School, professor (80136093)
NEMOTO Ken  The University of Tokushima, Institute of Health Bioscience Graduate School, assistant professor (10218274)
村上 圭史  徳島大学, 大学院ヘルスバイオサイエンス研究部, 助手 (10335804)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsS.intermedius / intermedilysin / bile duct cells / non-apoptotic cell death / Ca^<2+> oscillation / BiP / calcineurin / NFAT / S.intermedius / インターメディリシン / CD59 / カルシウム振動 / 非アポトーシス / PTEN / Lamin B1 / 自己免疫性肝疾患 / アポトーシス
Research Abstract

Streptococcus intermedius is a commensal member of the human oral, gastrointestinal and urinary floras, but may also be associated with deep-seated purulent infections, particularly in the liver abscess.
It was recently reported that the function of bacterial pore-forming toxins is biphasic. Not only do they act cytolytically on nucleated target cells when present in higher concentrations, but they can also affect signal-transduction pathways in cells when the toxin is present in low, sublytic concentrations. Intermedilysin (ILY), a human-specific pore-forming cytolysin, has been suggested as a potentially important virulence factor of S.intermedius.
Whereas Ca^<2+> is a key regulator of cell survival, the breakdown of Ca^<2+> homeostasis due to its sustained elevation was able to trigger cell death. The goals here were to examine whether a low, sublytic concentration of ILY affects Ca^<2+> homeostasis in human bile duct cells by induction of [Ca^<2+>]I oscillation and [Ca^<2+>]I related … More other cell responses (the activation of calcineurin/NFAT pathway, PI3/AKT/MTOR pathway, and endoplasmic reticulum stress).
Fron the calcium imaging, five rain ILY treatment generated an increase in[Ca^<2+>]i level from the average base line of 50 nM up to the average peak of 400 nM marked by two repeated oscillations every minute. Increased [Ca^<2+>]i was initially detected in the nuclei of ILY-treated cells subsequently followed with markedly increase in ER area. Immunocytochemistry and Westernbloting analysis, ILY treatment caused activation of calcineurin/NFAT1 signalling pathway and increased expression of AKT(p-S473),BiP, and PTEN. Interestingly the expression of BiP and AKT(p-S473)decreased in an hour post ILY treatment. Calcineurin inhibitor cyclosporine A prevented ILY-induced calcineurin/NFAT1 activation, cell death, and calcium oscillations.
ILY in concentration of 10-40 ng/ml capable of inducing calcium oscillations, activation of calcineurin/NFAT1 signalling pathway ; inactivation of PI3K/AKT/MTOR pathway, and caused ER stress disorder resulted non-apoptotic cell death in HuCCT1 cells. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (17 results)

All 2008 2007

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (7 results)

  • [Journal Article] A possible role of histone-like DNA-binding protein of Streptococcus intermedius in the pathogenesis of bile duct damage in primary biliary cirrhosis.2008

    • Author(s)
      Haruta I.
    • Journal Title

      Clin Immunol 127

      Pages: 245-251

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways.2008

    • Author(s)
      Liu D.
    • Journal Title

      Cell Microbiol 10

      Pages: 262-276

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The essentiality and involvement of Streptococcus intermedius histone-like DNA binding protein in bacterial viability and normal growth.2008

    • Author(s)
      Liu D.
    • Journal Title

      Mol Microbiol 68

      Pages: 1268-1282

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A possible role of histone-like DNA-binding protein of Streptococcus intermedius in the pathogenesis of bile duct damage in primary biliary cirrhosis2008

    • Author(s)
      Haruta, I., et. al.
    • Journal Title

      Clin Immunol 127

      Pages: 245-251

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways2008

    • Author(s)
      Liu, D., et. al.
    • Journal Title

      Cell Microbiol 10

      Pages: 262-276

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The essentiality and involvement of Streptococcus intermedius histone-like DNA binding protein in bacterial viability and normal growth2008

    • Author(s)
      Liu, D., et. al.
    • Journal Title

      Mol Microbiol 68

      Pages: 1268-1282

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A possible role of histone-like DNA-binding protein of Streptococcus intermedius in the pathogenesis of bile duct damage in primary biliarycirrhosis.2008

    • Author(s)
      Haruta I. et. al.
    • Journal Title

      Clin Immunol (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes viaactivation of ERK1/2 and JNK pathways2008

    • Author(s)
      Liu D.,et. al.
    • Journal Title

      Cell Microbiol 10

      Pages: 262-276

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intermedilysinによる培養ヒト胆管上皮細胞核膜抗原の異所性表出2007

    • Author(s)
      弘田克彦
    • Journal Title

      日本細菌学雑誌 62・1

      Pages: 106-106

    • NAID

      10019310191

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Investigation of the essentiality of histone-like protein in Streptococcus intermedius2007

    • Author(s)
      劉大力
    • Journal Title

      日本細菌学雑誌 62・1

      Pages: 138-138

    • Related Report
      2006 Annual Research Report
  • [Presentation] Intermedilysinにより誘導される非アポトーシス型細胞死と細胞内Ca^<2+>濃度の変動2008

    • Author(s)
      弘田 克彦
    • Organizer
      日本細菌学会総会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2008-03-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] The essentiality and involvements of Streptocuccus intermedius histone-like protein in bacterial viability and normal growth2007

    • Author(s)
      Liu Dali
    • Organizer
      The 2nd International Symposium on The Future Direction of Oral Sciences in the 21st Century
    • Place of Presentation
      Tokushima
    • Year and Date
      2007-12-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] NFAT1 activation in intermedilysin-induced human cholangiocellular carcinoma cell HuCCT12007

    • Author(s)
      Susilowati Heni
    • Organizer
      The 2nd International Symposium on The Future Direction of Oral Sciences in the 21st Century
    • Place of Presentation
      Tokushima
    • Year and Date
      2007-12-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Intermedilysin induces cell death in HepG2 cells2007

    • Author(s)
      Heni Susilowati
    • Organizer
      21st International Association for Dental Research-South East Asia Division
    • Place of Presentation
      Indonesia
    • Year and Date
      2007-09-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Intermedilysin induces cell death in HepG2 cells2007

    • Author(s)
      Heni, Susilowati, et. al.
    • Organizer
      21st International Association for Dental Research-South East Asia Division, Bali
    • Place of Presentation
      Indonesia
    • Year and Date
      2007-09-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The mechanisms of Intermedilysin to induce cell death on HepG2 and HuCCT1 cell lines2007

    • Author(s)
      Heni Susilowati
    • Organizer
      The 1st international symposium and workshop The Future Direction of Oral Sciences in the 21st century
    • Place of Presentation
      Awajishima
    • Year and Date
      2007-03-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Investigation of the toxicity of Streptococcus intermedius histone-like protein in Escherichia coli2007

    • Author(s)
      Liu Dali
    • Organizer
      The 1st international symposium and workshop The Future Direction of Oral Sciences in the 21st century
    • Place of Presentation
      Awajishima
    • Year and Date
      2007-03-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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