201. Ultraviolet B radiation generated platelet-activating factor receptor agonist formation involves EGF-R-mediated reactive oxygen species.
- Author
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Yao Y, Wolverton JE, Zhang Q, Marathe GK, Al-Hassani M, Konger RL, and Travers JB
- Subjects
- Animals, Dermatitis, Contact etiology, Dermatitis, Contact immunology, Dermatitis, Contact metabolism, Epithelial Cells immunology, Epithelial Cells metabolism, Epithelial Cells radiation effects, ErbB Receptors radiation effects, Humans, Immunosuppression Therapy, KB Cells, Mice, Mice, Hairless, Mice, Inbred C57BL, Platelet Activating Factor radiation effects, Platelet Membrane Glycoproteins biosynthesis, Reactive Oxygen Species pharmacology, Receptors, G-Protein-Coupled biosynthesis, Skin immunology, Skin metabolism, Skin radiation effects, ErbB Receptors physiology, Platelet Activating Factor metabolism, Platelet Membrane Glycoproteins agonists, Platelet Membrane Glycoproteins radiation effects, Reactive Oxygen Species metabolism, Reactive Oxygen Species radiation effects, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled radiation effects, Ultraviolet Rays
- Abstract
Recent studies have implicated the lipid mediator platelet-activating factor (PAF) in UVB-mediated systemic immunosuppression known to be a major cause for skin cancers. Previously, our group has demonstrated that UVB irradiation triggers the production of PAF and oxidized glycerophosphocholines that act as PAF-receptor (PAF-R) agonists. The present studies explored the mechanisms by which UVB generates PAF-R agonists. UVB irradiation of human epidermal KB cells resulted in both increased levels of reactive oxygen species (ROS) and PAF-R agonistic activity. Pretreatment of KB cells with antioxidants vitamin C and N-acetylcysteine or the pharmacological inhibitor PD168393 specific for the epidermal growth factor receptor all inhibited UVB-induced ROS as well as PAF-R agonists, yet had no effect on fMLP-mediated PAF-R agonist production. In addition, in vivo production of PAF-R agonists from UVB-irradiated mouse skin was blocked by both systemic vitamin C administration and topical PD168393 application. Moreover, both vitamin C and PD168393 abolished UVB-mediated but not the PAF-R agonist 1-hexadecyl-2-N-methylcarbamoyl glycerophosphocholine-mediated immunosuppression as measured by the inhibition of delayed type contact hypersensitivity to the chemical dinitrofluorobenzene. These studies suggest that UVB-induced systemic immunosuppression is due to epidermal growth factor receptor-mediated ROS which results in PAF-R agonist formation.
- Published
- 2009
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