Regulation of inflammation by homeostatic cholesterol transport pathways.

我们身体对感染和损伤的反应是由炎症集中调节的，炎症是一种保护性的生理反应，其特征是发红、肿胀、发热和疼痛，但有助于消除感染，清除死亡细胞和组织，并启动组织修复。然而，控制炎症的途径的扰动可能会导致几种慢性疾病，包括动脉粥样硬化、类风湿性关节炎和糖尿病等。因此，炎症需要得到严格控制。随着年龄的增长，我们调节不同生理过程的能力，包括我们如何处理饮食营养的能力下降，因此呈现出免疫系统以前看不到的新陈代谢结构。然而，尽管我们对炎症的主要驱动因素的了解有所增加，但调节炎症的详细代谢途径仍不清楚。这项建议的主要目的是了解胆固醇代谢如何调节炎症。胆固醇沉积增加通常是久坐不动的生活方式的结果，我们的研究表明，胆固醇也通过迄今未知的机制促进炎症过程的进展。我们将深入研究胆固醇是如何驱动炎症的，以及我们如何能够开发出预防或减缓这一事件的治疗方法。胆固醇对健康和治疗成本有重大影响，因为与之相关的心血管疾病风险。因此，了解胆固醇在炎症中的作用将有助于设计更好的策略来有效治疗疾病。

Our body's response to infection and injury is centrally regulated by inflammation, a protective physiological response which is characterized by redness, swelling, heat, and pain, yet helps eliminate infection, clear out dead cells and tissues, and initiate tissue repair. However, perturbations in pathways that control inflammation can give rise to several chronic diseases including atherosclerosis, rheumatoid arthritis, and diabetes amongst others. Therefore, inflammation needs to be tightly regulated. As we age, our ability to regulate different physiological processes, including how we process dietary nutrients, declines, therefore exhibiting metabolic configurations previously unseen by the immune system. Although our understanding of the major drivers of inflammation has increased, however, detailed metabolic pathways that regulate inflammation remain unknown. The main aim of this proposal is to understand how cholesterol metabolism regulates inflammation. Increased cholesterol deposition is often a consequence of sedentary lifestyle and our studies suggest that cholesterol also contributes to the progression of the inflammatory process through mechanisms hitherto unidentified. We will study in-depth how cholesterol drives inflammation and how we may be able to develop treatments to prevent or slow this event. Cholesterol has a significant impact on health and treatment costs because of the associated risk of cardiovascular disease. Thus, understanding the roles of cholesterol in inflammation will help design better strategies to treat disease effectively.