Ultraviolet B radiation of human skin generates platelet-activating factor receptor agonists.
Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production. In addition to cytokines, such as tumor necrosis factor-alpha (TNF-alpha), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous in vitro studies in keratinocytes or epithelial cell lines have demonstrated that UVB-mediated production of PAF agonists is due primarily to the pro-oxidative effects of this stimulant, resulting in the nonenzymatic production of modified phosphocholines (oxidized glycerophosphocholines). The current studies use human skin to assess whether UVB irradiation generates PAF-receptor agonists, and the role of oxidative stress in their production. These studies demonstrate that UVB irradiation of human skin results in PAF agonists, which are blocked by the antioxidant vitamin C and the epidermal growth factor receptor inhibitor PD168393. Inasmuch as UVB-generated PAF agonists have been implicated in animal model systems as being involved in photobiologic processes including systemic immunosuppression and cytokine (TNF-alpha) production, these studies indicate that this novel activity could be involved in human disease.
Travers
Jared B
JB
Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
Berry
Damien
D
Yao
Yongxue
Y
Yi
Qiaofang
Q
Konger
Raymond L
RL
Travers
Jeffrey B
JB
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D018384:Oxidative Stress; D010767:Phosphorylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000819:agonists; D011799:Quinazolines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D013997:Time Factors; D014466:Ultraviolet Rays
D000975:Antioxidants; C509204:PD168393; D010980:Platelet Membrane Glycoproteins; D011799:Quinazolines; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D010767:Phosphorylcholine; D001205:Ascorbic Acid