ROLE OF PROSTAGLANDINS IN INFLAMMATORY AND PROLIFERATIVE SKIN DISEASE

Experimental studies of relationships between prostaglandins and human skin have so far yielded results which are confusing and difficult to interpret. However, information on pathways for biosynthesis of prostaglandins, and on their actions at a cellular and molecular level promises to give a new insight into the role of prostaglandins in normal and diseased skin. Any discussion on prostaglandins must begin with a consideration of the biosynthetic pathways for prostaglandins. Prostaglandins are formed enzymatically from the parent 20carbon fatty acid arachidonic acid, as shown in Fig, 1. Arachidonic acid, in turn, is released from membrane phospholipid by the action of the lysosomal enzyme phospholipase A2• The microsomal enzyme cycloxygenase converts arachidonic acid via labile endoperoxide intermediates called prostaglandin G2 and prostaglandin H 2 to a number of prostaglandins with differing activities. Prostaglandin 12 is formed principally by vascular endothelium and causes vasodilation and inhibition of platelet aggregation (1). Thromboxane A2 is formed mainly by platelets and leads to platelet aggregation and adherence of platelets to vascular endothelium. In coronary heart disease the atheromatous endothelium is defective in production of prostaglandin 12 and thus thrombotic episodes occur. A similar deficiency of endothelial prostacyclin production underlies the thrombo-