title: Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites.
abstract: In the skin epidermis, the metabolism of polyunsaturated fatty acids (PUFAs) is highly active. Dietary deficiency of linoleic acid (LA), the major 18-carbon n-6 PUFA in normal epidermis, results in a characteristic scaly skin disorder and excessive epidermal water loss. Because of the inability of normal skin epidermis to desaturate LA to gamma-linolenic acid, it is transformed by epidermal 15-lipoxygenase to mainly 13-hydroxyoctadecadienoic acid, which functionally exerts antiproliferative properties in the tissue. In contrast, compared with LA, arachidonic acid (AA) is a relatively minor 20-carbon n-6 PUFA in the skin and is metabolized via the cyclooxygenase pathway, predominantly to the prostaglandins E(2), F(2)(alpha), and D(2). AA is also metabolized via the 15-lipoxygenase pathway, predominantly to 15-hydroxyeicosatetraenoic acid. At low concentrations, the prostaglandins function to modulate normal skin physiologic processes, whereas at high concentrations they induce inflammatory processes. PUFAs derived from other dietary oils are also transformed mainly into monohydroxy fatty acids. For instance, epidermal 15-lipoxygenase transforms dihomo-gamma-linolenic acid (20:3n-6) to 15-hydroxyeicosatrienoic acid, eicosapentaenoic acid (20:5n-3) to 15-hydroxyeicosapentaenoic acid, and docosahexaenoic acid (22:6n-3) to 17-hydroxydocosahexaenoic acid, respectively. These monohydroxy acids exhibit antiinflammatory properties in vitro. Thus, supplementation of diets with appropriate purified vegetable oils, fish oil, or both may generate local cutaneous antiinflammatory and antiproliferative metabolites which could serve as less toxic in vivo monotherapies or as adjuncts to standard therapeutic regimens for the management of inflammatory skin disorders.
authors.affiliation: Department of Dermatology, University of California, Davis 95616, USA. vaziboh@ucdavis.edu
authors.forename: V A
authors.initials: VA
authors.lastname: Ziboh
authors.forename: C C
authors.initials: CC
authors.lastname: Miller
authors.forename: Y
authors.initials: Y
authors.lastname: Cho
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004817:Epidermis / Q000201:enzymology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005395:Fish Oils / Q000627:therapeutic use; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D019787:Linoleic Acid / Q000378:metabolism; D008041:Linoleic Acids / Q000096:biosynthesis; D010938:Plant Oils / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D012871:Skin Diseases / Q000178:diet therapy / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D010938:Plant Oils; D011453:Prostaglandins; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; C024348:13-hydroxy-9,11-octadecadienoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D019787:Linoleic Acid; D001093:Arachidonate 15-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases