Functional analysis of BCL6 on allergic inflammation
| Project/Area Number |
14570404
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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 |
内科学一般
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
ARIMA Masafumi Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (00202763)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Akemi Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (90359597)
HATANO Masahiko Chiba University, Gene Research Center, Associate Professor, 遺伝子実験施設, 助教授 (20208523)
TOKUHISA Takeshi Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20134364)
岡田 誠治 熊本大学, エイズ学研究センター, 教授 (50282455)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | bronchial asthma / Th2 cytokine / lymphocyte / transcriptional repression / BCL6 / IL-5 / 好酸球 / アレルギー |
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| Research Abstract |
In terms of the factors regulating the magnitude of Th2 responses, we have been focusing on BCL6, a transcriptional repressor. It has been reported that Bcl6^<-/-> mice displayed pulmonary eosinophilic inflammation with augmentation of Th2 type cytokine production by T cells. Furthermore, we found that forced expression of BCL6 in lymphocytes through transgenesis downregulated Th2, cytokine production and prevented asthmatic response in sensitized mice. The regulatory mechanism of those cytokine productions by Bcl6 is controversial. When CD4^+ T cells from Bcl6-deficient and lck-Bcl6 transgenic mice were stimulated with anti-CD3 Abs, production of IL-5 among Th2 type cytokines was preferentially affected by the amount of Bcl6 in the T cells. We found a putative Bcl6-binding sequence (IL5BS) on the 3 untranslated region in the murine and human IL-5 genes, and specific binding of Bcl6 protein to the sequences was confirmed by chromatin immunoprecipitation assay and gel retardation assay. The binding of Bcl6 on the IL5BS was detected in Th1 and Th2 cells at resting stage. When those Th cells were stimulated with anti-CD3 Ab, the binding was still detected in Th1 cells but not in Th2 cells, The exogenous Bcl6 repressed expression of the reporter gene with, the IL5BS in K562 cells, and the repressor activity was lost by a point mutation of the IL5BS. Furthermore, the IL5BS was required for Bcl6 to repress expression of the exogenous IL-5 gene. Thus, the IL5BS may act as a silencer element for Bcl6 to repress expression of the IL-5 gene.
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Report
(3 results)
Research Products
(10 results)
