Ultraviolet B radiation generated platelet-activating factor receptor agonist formation involves EGF-R-mediated reactive oxygen species.
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.
Yao
Yongxue
Y
Department of Dermatology, and the Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Wolverton
Jay E
JE
Zhang
Qiwei
Q
Marathe
Gopal K
GK
Al-Hassani
Mohammed
M
Konger
Raymond L
RL
Travers
Jeffrey B
JB
D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D066246:ErbB Receptors / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D007165:Immunosuppression Therapy; D007624:KB Cells; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000528:radiation effects; D010980:Platelet Membrane Glycoproteins / Q000819:agonists* / Q000096:biosynthesis / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology / Q000528:radiation effects*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000096:biosynthesis / Q000528:radiation effects*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D066246:ErbB Receptors