Keystone Symposia

This meeting took place in 2001

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Eicosanoid Lipid Mediators: Biochemistry, Molecular Biology and Pharmacology and Cell-Cell Interactions in Inflammation (E6)

Organizer(s) William L. Smith, Marc Peters-Golden, Bengt Samuelsson, Charles N. Serhan and M. Amin Arnaout
April 7—12, 2001
Snowbird Resort • Snowbird, UT USA
Abstract Deadline: Dec 7, 2000
Late Abstract Deadline:
Scholarship Deadline:
Early Registration Deadline: Feb 7, 2001

Sponsored by The American Society of Nephrology

Summary of Meeting:
Eicosanoid Lipid Mediators: Biochemistry, Molecular Biology and Pharmacology: Eicosanoids include the prostanoid, leukotriene and epoxygenase metabolites of arachidonic acid. Regulating the production of prostanoids and leukotrienes has already been shown to have important clinical consequences in the treatment of chronic diseases. Currently, the two major research issues in the prostanoid area include determining why there are two cyclooxygenase isozymes and how these isozymes operate independently when co-expressed in the same cell. Research on these topics focuses on defining how cyclooxygenases-1 and -2 couple biochemically to upstream phospholipase A2s and to downstream PGH metabolizing enzymes and on how different prostanoid receptors may be involved in the actions of the specific PGHS isoforms. Major unresolved issues in the leukotriene area include defining the role of these products in host defense responses, the structural biology of leukotriene biosynthetic enzymes, and the biochemical bases for the mediator actions of leukotrienes. The long term outcome of these studies on prostanoids and leukotrienes is likely to be to extend the clinical usage of available cyclooxygenase and lipoxygenase inhibitors and leukotriene receptor antagonists and to facilitate the development of prostanoid receptor antagonists. The epoxygenase area is less well-developed. Epoxygenase metabolites include epoxy, monohydroxy and dihydroxy polyunsaturated fatty acids that are formed via the actions of P450s. These compounds may play key roles in regulating blood pressure and in local inflammatory responses, and thus, offer potentially important therapeutic targets. Key questions in the epoxygenase field involve defining the P450s relevant to epoxygenase metabolite formation and defining the specific epoxygenase metabolites which are of biological importance. Bringing together investigators studying a broad range of topics in eicosanoid biology and biochemistry is expected to lead to a more comprehensive understanding of the regulation of biosynthesis and mechanisms of actions of this class of lipid mediators. Cell-Cell Interactions in Inflammation: Lipid mediators play a pivotal role in acute and chronic inflammation. These small molecules not only play extracellular roles that govern cell-cell interactions and leukocyte traffic, but also play important roles as intracellular mediators of key signal transduction pathways relevant in inflammation and host defense. It is now clear that cell-cell interactions and adherence molecules on the surface of leukocytes and resident cells govern the transcellular biosynthesis of eicosanoid products including leukotrienes, lipoxins, and related substances. Not only is the biosynthesis of lipid mediators governed via cell-cell interactions, but the products also regulate cell-cell interactions critical in inflammation. Research on these topics focuses on defining the paracrine and autocrine signaling associated with cell trafficking critical in inflammation. Since inflammation is important in a variety of organs and diseases, presentations in this meeting will focus on the importance of novel therapeutic targets in the management of inflammatory responses with special reference to diseases that can impact renal function as well as inflammation in renal tissues. Recently a number of novel lipid mediators have been identified; their receptors and role in cell trafficking will be discussed. Also, development of new nonsteroidal agents that target cyclooxygenase 2-dependent prostanoids and signaling pathways have entered the clinical arena, and a more comprehensive understanding of these new inhibitors of lipid mediators and their impact in renal function and wound healing in human diseases will be discussed. This meeting is interfaced with the biochemistry, molecular biology, and pharmacology of eicosanoids in order to highlight recent advances in the identification of novel components of this important lipid mediator system with a special emphasis on the emergence of potential new therapeutic targets to manage these pathways. Hence, the intertwining of recent advances and research topics from the structural biology, molecular biology, and pharmacology of the eicosanoids with research topics on the vanguard of cell-cell interactions and inflammation should provide an exciting venue for basic scientists and clinician-scientists as well as clinicians who prescribe the use of antiinflammatory agents including traditional nonsteroidals as well as the new regime of COX-2 inhibitors.

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