| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Recent studies unraveled that cellular metabolism is tightly linked to activation of immune cells. While accumulation of extracellular/intracellular cholesterol has been shown to lead to macrophage activation and dysfunction, the underlying mechanisms remain incompletely understood. Here, we provide evidence that cellular cholesterol is required for macrophage activation. Accordingly, suppression of cholesterol accumulation by a novel supramolecular compound, polyrotaxane (PRX) inhibited Myd88-dependent macrophage inflammatory activation. Moreover, PRX treatment inhibited atherosclerotic plaque formation in Ldlr-/- mice. The finding that dynamic changes in cellular cholesterol directly regulate Myd88-dependent inflammatory programs in macrophages suggests the potential for new therapeutic and diagnostic approaches for chronic inflammatory diseases, such as atherosclerosis.
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