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

这个项目着眼于我们身体在对抗感染时产生的两种主要分子，一种是称为肿瘤坏死因子(TNF)的蛋白质，另一种是名为花生四烯酸的脂肪酸。在某些情况下，这些分子数量的持续增加会导致高度致残和衰弱的疾病，如类风湿性关节炎，这对我们的社区构成了巨大的负担。为了开发抗击这些疾病的药物，无论是接种疫苗还是抗炎药物，都需要明确定义炎症反应的关键成分。由于肿瘤坏死因子通过受体发挥作用，我们认为调节这种炎症反应的一个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(omega-6脂肪)与吞噬细胞相互作用，并导致该受体表达的戏剧性变化。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对观察结果进行透视。此外，将结合鱼油中发现的omega-3脂肪对这些炎症性疾病的保护作用来检验这一概念。

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.