Jackson 9307206 The isolation of prostaglandin(PG) was achieved by von Euler in 1932. In these experiments the first of many biological effects of the compound was discovered; the contraction of uterine smooth muscle. Since these early studies, PG has become recognized as a specific, highly active, short-lived local hormone synthesized in all mammalian cell systems. The local hormone is involved in lipid metabolism, insulin release, the regulation of cardiac function, body temperature and nervous system control, and the tissue inflammatory response. The overall objective of this research program is to determine the molecular mechanisms which operate in the regulation of cyclooxygenase (COX). The COX enzymes play central roles in PG biosynthesis by catalyzing the conversion of arachidonic acid and certain other 20 carbon polyunsaturated fatty acids. Additionally the role of factors IL-1 and TGF-Beta will be examined for their special effect on COX enzyme levels and turnover relative to PG synthesis. IL-1 and TGF-Beta are cytokines which appear to regulate transcriptional regulation of the COX genes. The present study will use human embryo lung fibroblasts and bovine pulmonary artery endothelial cells. Results will provide important information about regulatory mechanisms which govern PG synthesis. %%% This is a research project to study the complex mechanism which operates in mammalian systems to control prostaglandin formation. Prostaglandins are so called local hormones that are produced quickly in local tissue cells as a result of corporal stress, such as temperature changes, fatigue, or wounding. To begin to understand how the body produces the hormone and controls its level, we need to learn about the action of key enzymes that operate in its production. This control systems seems to be very complicated and involves the action of special components that operate to control reading messenger RNA(mRNA). mRNA contains the information the cells need t o form the enzyme for prostaglandin production. This research will help in our understanding about how the mammalian body controls its temperature and combats fatigue, how fat is formed and used, and how tissue becomes inflamed and irritated. ***
