CONFERENCE ON LIPID MEDIATORS

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The products of arachidonic acid metabolism are central to the inflammatory processes in bronchial asthma (leukotrienes) and in rheumatoid arthritis (prostaglandins) along with a diverse array of other pathobiologic states and physiologic functions. The introduction of novel therapies to prevent the biosynthesis or receptor-mediated action of the cysteinyl leukotrienes and of novel therapy selective for the induced prostaglandin endoperoxide synthetase type 2 (PGHS-2) has uncovered disease-related polymorphisms, additional disease prevention targets such as intestinal malignancy, and efficacy with reduced toxicity. At the same time, the use of gene disruption technology in the mouse has helped to define the functions of particular arachidonic acid metabolic pathways. The meeting planned will define the current controversies and insights provided by specific interventions in the human and gene disruption in the mouse, while concentrating at the cellular and molecular level on a variety of central evolving issues. These include: a clarification of the function in various cells of the ten or more phospholipase A2 (PLA2) species derived from separate genes and the compartmentalization of a particular PLA2 to its linked function with a particular perinuclear membrane associated enzyme; the transcriptional regulation of key enzymes in the eicosanoid generating pathways; and studies of gene polymorphism in association with disease states. There will also be a focus on the receptor proteins that appear to interact with arachidonic acid metabolites in two ways - within the nucleus for transcriptional regulation and at the plasma membrane for signal transduction responses. The program will assume reasonable state-of-the-art knowledge and will focus on the further implications of that knowledge and on the unresolved issues, using molecular, cellular, transgenic, and clinical approaches.