Guinea pig epidermis generates putative anti-inflammatory metabolites from fish oil polyunsaturated fatty acids.
Clinical studies have indicated that dietary fish oil may have therapeutic value in the treatment of psoriasis, a hyperproliferative, inflammatory skin disorder characterized by elevated LTB4. To evolve a possible mechanism for these beneficial effects, we determined the metabolic fate of fish oil derived n-3 fatty acids in the skin. Specifically, we incubated guinea pig epidermal enzyme preparations with [3H]eicosapentaenoic acid (20:5 n-3) and [14C]docosahexaenoic acid (22:6 n-3). Analyses of the radiometabolites revealed the transformation of these n-3 fatty acids into n-6 lipoxygenase (arachidonate 15-lipoxygenase) products: 15-hydroxyeicosapentaenoic acid (15-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDHE), respectively. Since 15-lipoxygenase products have been suggested as possible endogenous inhibitors of 5-lipoxygenase (an enzyme which catalyzes the formation of LTB4) we tested the ability of 15-HEPE and 17-HDHE in vitro to inhibit the activity of the 5-lipoxygenase. Incubations of these metabolites with enzyme preparations from rat basophilic leukemia (RBL-1) cells demonstrated that 15-HEPE (IC50 = 28 microM) and 17-HDHE (IC50 = 25 microM) are respectively potent inhibitors of RBL-I-5-lipoxygenase. The inhibitory potential of these fish oil metabolites provides a possible mechanism by which fish oil might act to decrease local cutaneous levels of LTB4, and thereby alleviate psoriatic symptoms.
Miller
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Department of Dermatology, School of Medicine, University of California, Davis 95616.
Yamaguchi
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Ziboh
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002851:Chromatography, High Pressure Liquid; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D004817:Epidermis / Q000201:enzymology / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D005395:Fish Oils / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D007975:Leukotriene B4 / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors; D008297:Male; D011565:Psoriasis / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D004281:Docosahexaenoic Acids; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid; C059164:15-hydroxy-5,8,11,13,17-eicosapentaenoic acid; D015118:Eicosapentaenoic Acid