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Molecular mechanisms of IL-8 gene expression by the immediate early gene products of cytomegelovirus

Research Project

Project/Area Number 09670320
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionKagoshima University (1999)
Kanazawa Medical University (1997-1998)

Principal Investigator

MURAYAMA Tsugiya  Faculty of Medicine, Kagoshima University, Associate Professor, 医学部, 助教授 (60159184)

Co-Investigator(Kenkyū-buntansha) 小渕 正次  金沢医科大学, 医学部, 助手 (70257450)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsCytomegalovirus / IL-8 / U373MG cell / luciferase reporter gene assay / NF-kB / AP-1 / ゲルシフトアッセイ / U373MG細胞 / 免疫染色 / 遺伝子導入 / THP-1細胞
Research Abstract

We previously observed that human cytomegalovires (CMV) infection induced a massive production of an interleukin-8 (IL-8) in a THP-1 cell. Hence, we examined the effect of CMV immediate early (IE) gene products on IL-8 production by the human astrocytoma cell line, U373MG. Transiently or stably transfection with CMV IE1 but not with CMV IE2 gene significantly augmented IL-8 protein secretion and IL-8 mRNA expression, compared with transfection with a control vector. Moreover, luciferase activity was enhanced in U373MG cells that were co-transfected with CMV IE1 and a chimeric firefly luciferase reporter genes driven by the transcriptional regulatory region of the human IL-8 gene. Furthermore, IE1 gene-mediated enhancement of luciferase activities was abolished by the introduction of the mutation into AP-1 or NF-kB factor binding elements in the regulatory region of the IL-8 gene, as previously observed on CMV infected cells. Finally, Western blotting as well as an immunohistochemical analysis demonstrated that CMV IE1 gene products increased the amount of p65 of NF-kB complexes translocated into the nuclei. Collectively, CMV IE1 gene expression may be sufficient to activates AP-1 and NF-kB, resulting in IL-8 gene expressions.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] T. Murayama: "Human cytomegakovirus induces interleukin-8 production by human monocytic cell line, THP-1, through acting concurrently on AP-1 and NF-kB binding sites of the interleukin-8 gene"J. Virol.. 71. 5692-5695 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. S. A. Khabar: "Interleukin-8 selectivery enhances cytopathic effect(CPE) induced by postivestrand RNA viruses in the human WISH cell line"Biochem. Biophis. Res. Commun.. 235. 774-778 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. S. A. Khabar: "The α chemokine, interleukin 8, inhibits the antiviral action of interferon α"J. Exp. Med.. 186. 1077-1085 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Murauyama: "Potential involvement of interleukin-8 (IL-8) in the pathogenesis of human cytomegalovirus infection"J. Leukocyte Biol.. 64. 62-67 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 村山次哉: "ヒトサイトメガロウイルス感染とケモカインの相互作用"日本臨床. 56. 69-74 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 村山次哉: "ヘルペスウイルスとケモカイン"血液・免疫・腫瘍. 3. 91-95 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 向田直史: "インターロイキン8の遺伝子発現調節機構"臨床病理. 46. 821-828 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. sadanari: "The effct of cyclic AMP on expression of the major immediate-early genes and replication of human cytomegalovirus in human central nervous system cell lines"arch. Virol.. 144. 1015-1025 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Murayama: "Human cytomegakovirus induces interleukin-8 production by human monocytic cell line, THP-1, through acting concurrently on AP-1 and NF-kB binding sites of the interleukin-8 gene."J.Virol.. 71(7). 5692-5695 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. S. A. Khabar: "Interleukin-8 selectivery enhances cytopathic effect (CPE ) induced by positive strand RNA viruses in the human WISH cell line."Biochem. Biophis. Res. Commun.. 235. 774-778 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. S. A. Khabar: "The α chemokine, interleukin 8, inhibits the antiviral action of interferon α."J. Exp. Med.. 186. 1077-1085 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Murayama: "Potential involvement of interleukin-8 (IL-8) in the pathogenesis of human cytomegalovirus infection"J. Leukocyte Biol.. 64. 62-67 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Murayama: "Interrelationship between human cytomegalovirus infection and chemokine"Nihonrinsho. 56(1). 69-74 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N. Mukaida: "Molecular mechanism of interleukin 8 gene expression."Rinshoubyouri. 46. 821-828 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H. Sadanari: "The effect of cyclic AMP on expression of the major immediate-early genes and replication of human cytomegalovirus in human central nervous system cell lines."Arch. Virol.. 144. 1015-1025 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Murayama,et al.: "Human cytomegalovirus induces interleukin-8......"J.Virol.. 71. 5692-5695 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.S.A.Khabar,et al.: "Interleukin-8 selectively enhances cytopathic effect....."Biochem.Biophis.Res.Commun.. 235. 774-778 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.S.A.Khabar,et al.: "The α chemokine,interleukin-8,inhibits the....."J.Exp.Med.. 186. 1077-1085 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] 村山次哉: "ヒトサイトメガロウイルス感染とケモカインの相互作用"日本臨床. 56. 69-74 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Murayama,et al.: "Potential involvement of IL-8 in the pathogenesis of....."J.Leukoc.Biol.. 64. 62-67 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 村山次哉: "ヘルペスウイルスとケモカイン"血液・免疫・腫瘍. 3. 91-95 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 向田直史、村山次哉: "インターロイキン8の遺伝子発現調節機構"臨床病理. 46. 821-828 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Sadanari et al.: "The effect of cyclic AMP on expression of the major....."Arch.Virol.. 144. 1015-1025 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 向田直史、村山次哉: "Biodefenceシリーズ3、異物認識と生体反応ー新しい視点を求めてー"日本生体防御学会、岡田秀親編集、菜根出版刊. 332 (1992)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Murayama et al.: "Potential involvement of IL-8 in the pathogenesis of ………" J.Leukoc.Biol.64. 62-67 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Sadanari et al.: "The effect of cyclic AMP on expression of the major ………" Arch.Virol.144. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 村山次哉: "ヘルペスウイルスとケモカイン" 血液・免疫・腫瘍. 3. 91-95 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 向田直史、村山次哉: "インターロイキン8の遺伝子発現調節機構" 臨床病理. 46. 821-828 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 向田直史、村山次哉: "Biodefence シリーズ3、異物認識と生体反応-新しい視点を求めて-" 日本生体防御学会、岡田秀親編集、菜根出版刊, 332 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Murayama,et al.: "Human cytomegalovirus induces interleukin-8 production……" J.Virol.71. 5692-5695 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.S.A.Khabar,et al.: "Interleukin-8 selectively enhances cytopathic effect(CPE)……" Biochem.Biophis.Res.Commun.235. 774-778 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.S.A.Khabar,et al.: "The α chemokine,interleukin-8,inhibits the antiviral action……" J.Exp.Med.186. 1077-1085 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 村山次哉: "ヒトサイトメガロウイルス感染とケモカインの相互作用" 日本臨床. 56. 69-74 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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