| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Outline of Final Research Achievements |
Macrophages are the major immune cells in the atherosclerotic lesions and play important roles in disease progression. Macrophages uptake oxidized low density lipoproteins (oxLDL) and differentiate into foam cells. Foam cells eventually undergo apoptosis or necroptosis. The former is thought to be protective, but the latter is thought to be detrimental. To develop new therapeutics for atherosclerosis, it is necessary to understand the molecular mechanisms of programmed cell death in macrophages and foam cells. In this study, I have investigated the roles of TAB2 and its close homolog TAB3 in macrophages and foam cells. Tab2/3-deficient foam cells underwent necrosis. In addition, TAB2, but not TAB3, was essential for suppression of TNF-induced necroptosis, which was responsible for the inflammasome activation in LPS-primed Tab2-deficient macrophages. These findings will help to develop novel strategies to treat atherosclerosis and other inflammatory diseases.
|
