Project/Area Number |
26860751
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Collagenous pathology/Allergology
|
Research Institution | Kobe University |
Principal Investigator |
|
Research Collaborator |
HASHIRAMOTO Akira
HASHIMOTO Teppei
SHIBANUMA Nao
NAKAGAWA Natsuko
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 関節リウマチ / 時計遺伝子 / 炎症性サイトカイン / シグナル伝達 |
Outline of Final Research Achievements |
I found a novel mechanism between inflammation and circadian rhythm in rheumatoid synovial cells as follows; ① A pro-inflammatory cytokine, Tumor necrosis factor-alpha (TNF-α) reduced the mRNA expression of a circadian core clock gene, Per2, and induced those of Bmal1. However, TNF-α did not affect the oscillation of Bmal1 gene expression.② Up-regulation of Bmal1 gene, induced by TNF-α, was associated with ROR alpha, an activator of Bmal1 gene expression. ③These results were cancelled by an intracellular calcium chelator, BAPTA-AM but not a calcineurin inhibitor FK-506, suggesting that TNF-α-induced up-regulation of Bmal1 gene is independent of a transcriptional factor NFAT.
|