| Project/Area Number |
16390233
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Chiba University Graduate school of Medicine |
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Principal Investigator |
ARIMA Masafumi Chiba University, Graduate school of Medicine, Lecturer, 大学院・医学研究院, 講師 (00202763)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUHISA Takeshi Chiba University, Graduate school of Medicine, Professor, 大学院・医学研究院, 教授 (20134364)
HATANO Masahiko Chiba University, Biomedical Center, Associate Professor, バイオメディカルセンター, 助教授 (20208523)
SAKAMOTO Akemi Chiba University, Graduate school of Medicine, Research Associate, 大学院・医学研究院, 助手 (90359597)
FUJIMURA Lisa Chiba University, Biomedical Center, Research Associate, バイオメディカルセンター, 助手 (30376363)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | BCL6 / transcriptional repressor / Pulmonary fibrosis / Apoptosis / alveolar epithelial cell / chemokine / chromatin remodeling / 間質性肺炎 / 線維化 / 遺伝子欠損マウス / 遺伝子導入マウス / 細胞死 / トランスジェニックマウス / ノックアウトマウス |
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| Research Abstract |
Many CC-type chemokine genes are located in a chemokine gene cluster at the chromosome 17q11.2 and at 11q21.2 in humans in mice, respectively. These clusters include genes encoding CCL2-CCL7-CCL11-CCL8-CCL13-CCL1 in humans and CCL2-CCL7-CCL11-CCL12-CCL8-CCL1 in mice. The similar synteny in the cluster between humans and mice may be orchestrated by the conserved machinery. Since CCL2 is known to be negatively regulated by a transcriptional repressor Bcl6 and some putative Bcl6-binding sequences are observed in the clusters, we examined the role of Bcl6 in expression of these chemokine genes in the cluster. Here we show that the amount of these chemokine mRNAs except CCL12 mRNA increased strikingly in lung tissues and bronchoalveolar lavage fluid cells from Bcl6-deficient mice as compared with that from control mice. Down-regulation of Bcl6 in human alveolar epithelial cells (A549) and human embryonic kidney cells (HEK293T) up-regulated expression of these chemokine genes. Furthermore, chromatin modifications such as acetylation and methylation of histone, and Bcl6-binding to the sequences in the cluster were observed in each cell line by chromatin immunoprecipitation assay. Thus, Bcl6 plays an important role in the coordinated regulation of these chemokine genes as a transcriptional repressor.
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