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

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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.