2002 Fiscal Year Final Research Report Summary
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
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Nagasaki 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
|
| Keywords | Cytochrome b558 / STAT-1alpha / IFN-gamma / IRF-1 / CYBB / Transcription |
|---|
| 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.
|
Research Products
(6 results)
-
-
-
-
[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
-
-
[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
