| Project/Area Number |
25840001
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Molecular biology
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
H. KOBAYASHI Eri 東北大学, 医学(系)研究科(研究院), 助教 (70634971)
|
|---|
| Project Period (FY) |
2013-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 転写制御 / 炎症 / ストレス応答 / ChIP-seq / 遺伝子発現制御 / Nrf2 / マクロファージ / 状況特異的 |
|---|
| Outline of Final Research Achievements |
Nrf2 is a key transcription factor that regulates oxidative/xenobiotic stress-response and prevention/resolution of inflammation. However, the mechanisms how Nrf2 prevent inflammation or how Nrf2 target genes contribute to the anti-inflammatory process are still unclear. Here we demonstrate that Nrf2 represses lipopolysaccharide-induced expression of proinflammatory cytokines, including Il6, Il1b and Il1a, which exacerbate inflammation. ChIP-seq analysis revealed that Nrf2 binds to the proximity of Il6, Il1b and Il1a genes. The Nrf2-mediated transcriptional repression of proinflammatory genes was independent from the inducers or inhibitors of reactive oxygen species accumulation. Thus, contrary to the widely accepted view that Nrf2 is an activator of transcription, our results demonstrate that Nrf2-mediated anti-inflammation is achieved through direct transcriptional repression of proinflammatory cytokine genes by Nrf2.
|
