Regulation of TNF receptor expression by omega-6 and omega-3 polyunsaturated fatty acids

这个项目着眼于我们的身体在试图对抗感染时产生的两种主要分子，一种叫做肿瘤坏死因子（TNF）的蛋白质和一种叫做花生四烯酸的脂肪酸。在某些情况下，这些分子的持续产生会导致高度致残和衰弱的疾病，如类风湿性关节炎，这给我们的社区带来了巨大的负担。为了开发对抗这些疾病的药物，无论是疫苗接种还是抗病毒药物，都需要明确定义炎症反应的关键组成部分。由于TNF通过受体起作用，我们认为调节这种炎症反应的关键问题是免疫系统细胞上这些受体表达的变化。我们的初步工作表明，脂质分子如花生四烯酸（ω-6脂肪酸）与吞噬细胞相互作用，并导致这种受体表达的巨大变化。我们的研究计划将更详细地研究这一点，并根据炎症反应和相关疾病的参数进行观察。此外，这一概念将在鱼油中发现的omega-3脂肪对这些炎症性疾病的保护作用方面进行研究。

This project looks at two major molecules which our body generates in trying to combat infections, a protein called tumor necrosis factor (TNF) and a fatty acid called arachidonic acid. In some cases the persistent production of elevated amounts of these molecules leads to highly crippling and debilitating diseases , such as rheumatoid arthritis, which pose a huge burden to our community. To develop medication to combat these diseases be it either vaccination or antiinflammatory drugs, there is a need to clearly define key components of the inflammatory response. Since TNF acts through a receptor we propose that a critical issue in the regulation of this inflammatory response is the changes in the expression of these receptors on cells of the immune system. Our preliminary work suggests that lipid molecules such as arachidonic acid (omega-6 fat) interacts with phagocytic cells and causes drammatic changes to the expression of this receptor. Our research proposal will look at this in more detail and place the observation into perspective in terms of parameters of the inflammatory reaction and associated diseases. Furthermore this concept will be examined in relation to the protective effects which the omega-3 fats found in fish oil have on these inflammatory diseases.