Dermis-derived 15-hydroxy-eicosatetraenoic acid inhibits epidermal 12-lipoxygenase activity.
The purpose of the present study was to analyze the metabolism of arachidonic acid (AA) in normal human dermis. After incubating homogenized dermis with exogenous AA, the extracted lipids were isolated by reversed-phase high-performance liquid chromatography. Each chromatographic peak was characterized by its UV absorption spectrum and identified by its coelution with the appropriate authentic standard and by radioimmunoassay of its eluate fraction. Identified compounds were quantitated by integrated optical density. Homogenized human dermis transformed AA into both cyclooxygenase and lipoxygenase products, but predominantly 15-hydroxy-eicosatetraenoic acid (15-HETE). Cultured fibroblasts from normal human dermis also mainly metabolized AA into 15-HETE. To determine whether dermis-derived 15-HETE might modify the AA metabolism of epidermis, normal human epidermis was incubated with dermis. Increasing amounts of dermis resulted in an increasing inhibition of epidermal 12-HETE formation. Similarly, 15-HETE alone induced a dose-dependent decrease of epidermal 12-HETE formation, while the formation of prostaglandin E2 was unchanged. Since 12-HETE possess the ability to elicit skin inflammation and to stimulate epidermal DNA synthesis, 15-HETE formation may be a way whereby dermis regulates important epidermal activities.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004817:Epidermis / Q000201:enzymology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D012867:Skin / Q000033:anatomy & histology; D012879:Skin Physiological Phenomena
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases