Nitric oxide and peroxynitrite released by ultraviolet B-irradiated human endothelial cells are possibly involved in skin erythema and inflammation.
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.
Deliconstantinos
G
G
Department of Experimental Physiology, University of Athens Medical School, Greece.
Villiotou
V
V
Stavrides
J C
JC
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
D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase