title: Nitric oxide and peroxynitrite released by ultraviolet B-irradiated human endothelial cells are possibly involved in skin erythema and inflammation.
abstract: In this study we attempted to demonstrate whether endothelial cell nitric oxide synthase (eNOS) and xanthine oxidase (XO) could be activated to release nitric oxide (NO) and peroxynitrite (ONOO-) following exposure to ultraviolet B (UVB) radiation and to define whether this light-induced response could be involved in the pathogenesis of sunburn erythema and inflammation. Treatment of human endothelial cells with UVB (290-320 nm) radiation (up to 100 mJ/cm2) resulted in an increase of both NO and ONOO- release that was inhibited by NG-monomethyl-L-arginine (L-NMMA). Treatment of cell cytosol with various doses of UVB radiation (up to 20 mJ/cm2) resulted in a threefold increase of XO activity that was inhibited (approximately 90% by oxypurinol. In reconstitution experiments, when purified eNOS was added to purified XO, an almost fourfold increase in ONOO- production at 20 mj/cm2 UVB radiation was observed. UVB radiation (100 mg/cm2) decreased cell membrane fluidity, indicating changes in the physicochemical characteristics of the membranes. In in vivo experiments, when human volunteers were subjected to UVB light, a protection factor (PF) of 3.90 +/- 0.85 was calculated when an emulsified cream formulation containing nitro-L-arginine (L-NA; 2%) and L-NMMA (2%) was applied to their skin. The present studies indicate that UVB radiation acts as a potent stimulator of eNOS and XO in human endothelial cells. The cytotoxic effects of NO and ONOO- may be the main factors in the integrated response of the skin leading to vasodilatation, the first key event of erythema production and the inflammation process.
authors.affiliation: Department of Experimental Physiology, University of Athens Medical School, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Deliconstantinos
authors.forename: V
authors.initials: V
authors.lastname: Villiotou
authors.forename: J C
authors.initials: JC
authors.lastname: Stavrides
mesh_terms: D002478:Cells, Cultured; D003872:Dermatitis / Q000209:etiology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000528:radiation effects*; D004789:Enzyme Activation; D004890:Erythema / Q000209:etiology / Q000378:metabolism; D006801:Humans; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013471:Sunburn / Q000150:complications; D014466:Ultraviolet Rays; D014471:Umbilical Veins / Q000378:metabolism / Q000528:radiation effects; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase