Ultraviolet B Radiation Generated Platelet-Activating Factor Receptor Agonist Formation Involves EGF-R-Mediated Reactive Oxygen Species
Open Access
- 1 March 2009
- journal article
- Published by The American Association of Immunologists
- Vol. 182 (5), 2842-2848
- https://doi.org/10.4049/jimmunol.0802689
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.Keywords
This publication has 51 references indexed in Scilit:
- UVB Radiation-Mediated Inhibition of Contact Hypersensitivity Reactions Is Dependent on the Platelet-Activating Factor SystemJournal of Investigative Dermatology, 2008
- Inhibition of Photocarcinogenesis by Platelet-Activating Factor or Serotonin Receptor AntagonistsCancer Research, 2008
- Platelet-Activating Factor Is Crucial in Psoralen and Ultraviolet A-Induced Immune Suppression, Inflammation, and ApoptosisThe American Journal of Pathology, 2006
- Epidermal Growth Factor Receptor-dependent, NF-κB-independent Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Inhibits Ultraviolet Irradiation-induced Caspases-3, -8, and -9 in Human KeratinocytesJournal of Biological Chemistry, 2003
- Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader11Mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee by the United States Department of Agriculture and does not imply its approval to the exclusion of other products that may be suitable.Free Radical Biology & Medicine, 1999
- Platelet-activating factor receptor: gene expression and signal transductionBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1995
- Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells.JCI Insight, 1995
- Suppressor T Lymphocytes Control the Development of Primary Skin Cancers in Ultraviolet-Irradiated MiceScience, 1982
- Suppression of contact hypersensitivity by ultraviolet radiation: An experimental modelSpringer Seminars in Immunopathology, 1981
- A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATIONCanadian Journal of Biochemistry and Physiology, 1959