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Epidermal Platelet-activating Factor Receptor Activation and Ultraviolet B Radiation Result in Synergistic Tumor Necrosis Factor-alpha Production |
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| Authors: | Jay E. Wolverton Mohammed Al-Hassani Yongxue Yao Qiwei Zhang Jeffrey B. Travers |
| Affiliation: | Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN; Department of Pediatrics and the H.B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN; Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN; Richard L. Roudebush V.A. Medical Center, Indiana University School of Medicine, Indianapolis, IN |
| Abstract: | Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production which has been implicated in photoaggravated dermatoses. In addition to cytokines such as tumor necrosis factor-α (TNF-α), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous studies have demonstrated that UVB-mediated production of keratinocyte TNF-α is in part due to PAF. The current studies use a human PAF-receptor (PAF-R) negative epithelial cell line transduced with PAF-Rs and PAF–R-deficient mice to demonstrate that activation of the epidermal PAF-R along with UVB irradiation results in a synergistic production of TNF-α. It should be noted that PAF-R effects are mimicked by the protein kinase C (PKC) agonist phorbol myristic acetate, and are inhibited by pharmacological antagonists of the PKC gamma isoenzyme. These studies suggest that concomitant PAF-R activation and UVB irradiation results in a synergistic production of the cytokine TNF-α which is mediated in part via PKC. These studies provide a novel potential mechanism for photosensitivity responses. |
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