title: Eicosapentaenoic acid, a n-3 polyunsaturated fatty acid differentially modulates TNF-alpha, IL-1alpha, IL-6 and PGE2 expression in UVB-irradiated human keratinocytes.
abstract: In response to UVB-irradiation keratinocytes release a variety of cytokines and prostaglandins, including tumor necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6), and prostaglandin E2 (PGE2). n-3 Polyunsaturated fatty acids (PUFA), mainly present in fish oil, can modulate cytokine synthesis, as predominantly studied in macrophages. In order to investigate the immune modulating actions of n-3 PUFA on the UVB response in human skin, we investigated the effect of eicosapentaenoic acid (EPA), a n-3 PUFA and a precursor of eicosanoid biosynthesis, on UVB-modulated TNF-alpha, IL-1alpha, IL-6, and PGE2 expression in normal human keratinocytes (NHK). We show that cultured NHK can efficiently take up EPA. Basal TNF-alpha expression is very low in NHK. IL-1alpha on the contrary is significantly present in untreated cultured NHK. Upon UVB-irradiation (32 mJ per cm2) TNF-alpha mRNA expression and secretion is induced and IL-1alpha mRNA expression is reduced, although IL-1alpha secretion is induced. EPA treatment results in higher TNF-alpha and IL-1alpha expression, both in nonirradiated and UVB-irradiated keratinocytes. Moreover EPA and UVB appear to act synergistically to superinduce TNF-alpha expression. EPA treatment results also in lipid peroxidation and in decreased PGE2 and IL-6 secretion after UVB-irradiation. In contrast to EPA, oleic acid (monounsaturated fatty acid) and linoleic acid (n-6 PUFA) treatment did not result in higher TNF-alpha or IL-1alpha levels in nonirradiated or UVB-irradiated NHK, indicating that the observed effects are specific for EPA. In conclusion, these results show that EPA can differentially modulate UVB-induced cytokine and prostaglandin synthesis in NHK.
authors.affiliation: Department of Dermatology, Katholieke Universiteit Leuven, Belgium.
authors.forename: Annemie
authors.initials: A
authors.lastname: Pupe
authors.forename: Ralf
authors.initials: R
authors.lastname: Moison
authors.forename: Petra
authors.initials: P
authors.lastname: De Haes
authors.forename: Gerard Beijersbergen
authors.initials: GB
authors.lastname: van Henegouwen
authors.forename: Lesley
authors.initials: L
authors.lastname: Rhodes
authors.forename: Hugo
authors.initials: H
authors.lastname: Degreef
authors.forename: Marjan
authors.initials: M
authors.lastname: Garmyn
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics*; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000187:drug effects; D014280:Triglycerides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014466:Ultraviolet Rays
chemical_list: D001095:Arachidonic Acids; D017077:Culture Media, Conditioned; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D000960:Hypolipidemic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C077446:Pikasol; D015232:Dinoprostone