Induction of Tumor Necrosis Factor–α by UVB: A Role for Reactive Oxygen Intermediates and Eicosanoids

• Published in: Photochemistry and photobiology 2003-07, Vol.78 (1), p.68-74
• Main Authors: Pupe, Annemie, Degreef, Hugo, Garmyn, Marjan
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; Cyclooxygenase Inhibitors - metabolism; Eicosanoids - physiology; ENVIRONMENTAL PHOTOBIOLOGY AND UVR EFFECTS; Ferrous Compounds - pharmacology; Humans; Hydrogen Peroxide - pharmacology; Keratinocytes - enzymology; Lipoxygenase - metabolism; NF-kappa B - physiology; Oxidative Stress; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; Signal Transduction; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Ultraviolet Rays
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1562/0031-8655(2003)078<0068:IOTNFB>2.0.CO;2

UVB irradiation induces nuclear factor–κB (NF-κB) activation, tumor necrosis factor–α (TNF-α) expression and reactive oxygen intermediates (ROI) in keratinocytes. We investigated whether ROI play a role in UVB-induced TNF-α mRNA expression. The antioxidants N-acetyl cysteine, NAC, epigallocathin gallate, EGCG, butylated hydroxyanisole (BHA) and vitamin C could reduce UVB-induced TNF-α mRNA levels to various degrees; vitamin E (α-tocopherol) had no effect. BHA was the most potent inhibitor. The oxidant tertiary butylated hydroperoxide could effectively induce TNF-α mRNA expression. Nordihydroguaiaretic acid (NDGA) and MK-886, inhibitors of lipoxygenase (LOX), and indometacin and quinacrine, inhibitors of cyclooxygenase (COX) and phospholipase A2, respectively, could also reduce UVB-induced TNF-α mRNA expression. Inhibition by NDGA was in concordance with the results for BHA. NDGA, indometacin, quinacrine and BHA could also effectively inhibit the inhibitor of NF-κB degradation, thereby maintaining NF-κB inactivity. In conclusion, we show that ROI are implicated in the induction of TNF-α mRNA by UVB and that not all antioxidants are equally effective inhibitors. COX products and more importantly LOX products, which themselves are products of an oxidative metabolism, are the main ROI implicated in this induction of TNF-α expression by UVB probably via activation of NF-κB.