Author:

Keywords:

Antilipemic Agents, Arachidonic Acids, Cells, Cultured, Culture Media, Conditioned, Cytokines, Dinoprostone, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Gene Expression, Humans, Interleukin-1, Interleukin-6, Keratinocytes, Lipid Peroxidation, Triglycerides, Tumor Necrosis Factor-alpha, Ultraviolet Rays, Science & Technology, Life Sciences & Biomedicine, Dermatology, EPA, PUFA, ultraviolet radiation, TUMOR-NECROSIS-FACTOR, ULTRAVIOLET-B, FISH-OIL, PROSTAGLANDIN SYNTHESIS, CYTOKINE NETWORK, CELLS, LIGHT, SUPPLEMENTATION, INTERLEUKIN-6, PROLIFERATION, Hypolipidemic Agents, 1103 Clinical Sciences, 1112 Oncology and Carcinogenesis, Dermatology & Venereal Diseases, 3202 Clinical sciences

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.