Analysis of mechanisms for the effective treatment of IFN-gamma for a chronic granulomatous disease caused by the defects in CYBB transcription
| Project/Area Number | 13670220 |
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Nagasaki University |
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Principal Investigator |
KAMATORI Atsushi Institute of Tropical Medicine, Assistant Professor, 熱帯医学研究所, 講師 (60244092)
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 章一 長崎大学, 熱帯医学研究所, 助手 (40253695)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed(Fiscal Year 2002)
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| 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)
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| Keywords | Cytochrome b558 / STAT-1alpha / IFN-gamma / IRF-1 / CYBB / Transcription / STAT-1 |
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| 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.
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Report
(3results)
Research Products
(9results)
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[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)
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Related Report
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[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
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Related Report
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