Epidermal platelet-activating factor receptor activation and ultraviolet B radiation result in synergistic tumor necrosis factor-alpha production.
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-alpha (TNF-alpha), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous studies have demonstrated that UVB-mediated production of keratinocyte TNF-alpha 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-alpha. 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-alpha which is mediated in part via PKC. These studies provide a novel potential mechanism for photosensitivity responses.
Wolverton
Jay E
JE
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
Al-Hassani
Mohammed
M
Yao
Yongxue
Y
Zhang
Qiwei
Q
Travers
Jeffrey B
JB
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014466:Ultraviolet Rays
D016207:Cytokines; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; D011493:Protein Kinase C