Ultraviolet B and H2O2 Are Potent Inducers of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes

Abstract

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is strongly expressed by epidermal keratinocytes during wound healing, in psoriasis, and in bullous diseases such as erythema multiforme and bullous pemphigoid. All of these disorders are characterized by increased microvascular permeability and angiogenesis. Since the development of erythema as a result of hyperpermeable blood vessels is also a common feature after excess sun exposure, we speculated about an up-regulation of VEGF expression by ultraviolet (UV) light. To test this hypothesis, we analyzed the effect of UVB irradiation on VEGF expression in cultured keratinocytes. Thereby we found a large increase in VEGF mRNA and protein levels upon irradiation of quiescent keratinocytes with sublethal and physiologically relevant doses of UVB. Although H2O2 was also a potent inducer of VEGF expression, the effect of UVB irradiation is unlikely to be mediated by reactive oxygen species as determined by the use of antioxidants. Further experiments revealed that the UVB-induced overexpression of VEGF is dependent on de novo protein synthesis and might occur via release of soluble mediators, which subsequently turn on VEGF expression. In summary, our results suggest a novel role of VEGF in the induction of erythema after excess sun exposure.