| 研究課題/領域番号 |
18K18194
|
|---|
| 研究機関 | 広島大学 |
|---|
研究代表者 |
ZAHARIEVA ELENA 広島大学, 原爆放射線医科学研究所, Specially Appointed Assistant Professor (30766697)
|
|---|
| 研究期間 (年度) |
2018-04-01 – 2021-03-31
|
| キーワード | cardio-vascular disease / low dose rate radiation / low dose radiation / inflammatory cytokines / monocyte adhesion / adhesion molecules / chronic inflammation |
|---|
| 研究実績の概要 |
After dose and dose-rate dependencies of radiation-induced vascular-monocyte interaction were established, the underlying mechanisms were explored by inhibition of the NF-kB pathway or siRNA knockdown of adhesion molecules and major cytokines. The results indicated a strong implication of the NF-kB pathway and Intercellular Adhesion Molecule-1 in radiation-induced inflammation. Comparative functional adhesion assays under static or dynamic conditions suggested that the firm arrest of monocytes on the endothelial surface might be the critical step in initiation of cardiovascular lesions.
In addition, time-course experiments suggested that soluble and cell surface inflammatory factors remain upregulated more than 10 days after radiation exposure-longer than previously thought.
|
| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
The project is progressing mostly according to the original plans.
In FY2019 most of the efforts were directed towards identifying molecular mediators of radiation-induced inflammation, which may lead to cardiovascular disease.
Efforts were also directed towards establishing and validating techniques necessary for the experiments in FY2020 and preparations for these experiments are now completed.
|
| 今後の研究の推進方策 |
In the next stage of this project the inflammatory profile after low dose/low dose rate gamma irradiation will be compared between human and mouse vascular models. Radiation-induced lesions in the murine vasculature will be quantified, in order to estimate the dose and dose rate effects.
Human in vitro models will continue to be interrogated by siRNA and high-throughput imaging experiments, in order to reveal the molecular mechanisms behind low dose/low dose rate radiation-induced endothelial-monocyte arrest. In addition to NF-kB, the role of other stress pathways will be investigated.
The comparative expression of inflammatory factors in human and mouse models after low dose/low dose rate radiation, will allow us to draw conclusions on the possible extrapolation of animal data to humans.
|
| 次年度使用額が生じた理由 |
The experimental plan for FY2020 has been slightly changed, with some experiments now scheduled for several months later. For this reason the reagents and consumables needed for these experiments have not been purchased in the end of FY2019 and will be purchased in the beginning of FY2020.
|
