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Analysis of mechanisms for the effective treatment of IFN-gamma for a chronic granulomatous disease caused by the defects in CYBB transcription

Research Project

Project/Area Number 13670220
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNagasaki University

Principal Investigator

KAMATORI Atsushi  Institute of Tropical Medicine, Assistant Professor, 熱帯医学研究所, 講師 (60244092)

Co-Investigator(Kenkyū-buntansha) 鈴木 章一  長崎大学, 熱帯医学研究所, 助手 (40253695)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsCytochrome b558 / STAT-1alpha / IFN-gamma / IRF-1 / CYBB / Transcription / STAT-1
Research Abstract

Interferon (IFN)-gamma induces the expression of the gp91phox gene both during myeloid differentiation and also in mature phagocytes through several cis-elements and their binding proteins. To find new cis-elements for this induction, transient expression assays were performed using a reporter gene driven by serially truncated gp91phox promoters in U937 cells. The results suggest that a critical cis-element for induction exists in the region from bp -115 to -96 of the promoter. Site-directed mutagenesis showed that a gamma -activated sequence (GAS) element at bp -100 (-100GAS) of the gp91phox promoter plays a pivotal role for the IFN-gamma -dependent activity of the bp -115 to +12 region of the gp91phox promoter. Electrophoretic mobility shift assays using several GAS competitors and specific antibodies indicated that phosphorylated STAT-1 alpha specifically binds to the -100GAS. Site-directed mutagenesis showed that an interferon-stimulated response element (ISRE) at bp -88 (-88ISRE) mediates the induction of the gene by IFN-gamma in cooperation with -100GAS. Electrophoretic mobility shift assay showed that IRF-1 dominantly binds to -88ISRE in an IFN-gamma -dependent fashion. These results demonstrate a new mechanism for IFN-gamma -induced transcription of the gp91phox gene by the cooperation of STAT-1alpha and IRF-1 binding to -100GAS and -88ISRE, respectively.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Atsushi Kumatori, et al.: "Cooperation of STAT-1 and IRF-1 in IFN-γ-induced transcription of the gp91phox gene"The Journal of Biological Chemistry. 277巻・11号. 9103-9111 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Islam, M.R., et al.: "PU.1 Is Dominant and HAF-1 Supplementary for Activation of the gp91(phox) Promoter in Human Monocytic PLB-985 Cells"J Biochemistry (Tokyo). 131巻・4号. 533-540 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harada, M., et al.: "Superoxide-dependent and -independent pathways are involved in the transmission blocking of malaria"Parasitology Research. 87巻・8号. 605-608 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Islam, M.R., Fan, C., Fujii, Y., Hao, L.J., Suzuki, S., Kumatori, A., Yang, D., Rusvai, E., Suzuki, N., Kikuchi, H., and Nakamura, M.: "PU.1 Is Dominant and HAF-1 Supplementary for Activation of the gp91(phox) Promoter in Human Monocytic PLB-985 Cells"J Biochem. (Tokyo), 131. 533-540 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumatori, A., Yang, D., Suzuki, S., and Nakamura, M.: "Cooperation of STAT-1 and IRF-1 in Interferon-gamma-induced Transcription of the gp91^<phox> Gene"J Biol Chem. 277. 9103-9111 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Harada, M., Owahashi, M., Suguri, S., Kumatori, A., Nakamura, M., Kanbara, H., Matsuoka, H., and Ishii, A.: "Superoxide-dependent and-independent pathways are involved in the transmission blocking of malaria"Parasitol Res. 87. 605-608 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Atsushi Kumatori, et al.: "Cooperation of STAT-1 and IRF-1 in IFN-γ-induced transcription of the gp91phox gene"The Journal of Biological Chemistry. 277巻・11号. 9103-9111 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Islam, M.R., et al.: "PU.1 Is Dominant and HAF-1 Supplementary for Activation of the gp91(phox) Promoter in Human Monocytic PLB-985 Cells"J Biochem (Tokyo). 131巻. 533-540 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Atsushi Kumatori et al.: "Cooperation of STAT-1 and IRF-1 IFN-γ-induced transcription of the gp91phox gene"The Journal of Biological Chemistry. (In press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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