Eicosapentaenoic Acid, a n-3 Polyunsaturated Fatty Acid Differentially Modulates TNF-α, IL-1α, 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.

Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts

“…PGE 2 is more mitogenic and proinflammatory than PGE 3 . It has been reported that fish oils, rich in -3 PUFAs, possess anti-inflammatory properties in UV-exposed skin (15). Recently, EPA and DHA were reported to reduce basal and UV-induced interleukin-8 secretion by keratinocytes and fibroblasts (16).…”

Impact of Supplementing Preoperative Intravenous Omega 3 Fatty Acids in Fish Oil on Immunomodulation in Elderly Patients Undergoing Hip Surgery

“…Supplementation with omega-3 fatty acids also results in the generation of three-series prostanoids and reduces release of PGE2 [20]. The omega-3 fatty acids compete with AA for their phospholipase-mediated release from membranes [21] and for metabolism of the free fatty acids by cyclo-oxygenase and lipoxygenase [22].…”

The Protective and Recovery Effects of Fish Oil Supplementation on Cedar Pollen-Induced Allergic Reactions in Mice

“…DHA and EPA enhance TNF-α and IL-6 secretion in macrophages [15][16][17], and dietary fish oil supplementation increases serum TNF-α concentration in response to endotoxin challenges [15]; thus, n-3 PUFAs are regarded as pro-inflammatory factors. Treatment with n-3 PUFAs also increases TNF-α, IL1a, and IL-6 expression in adipocytes, keratinocytes, splenocytes, and hepatocytes [18][19][20][21][22].…”