ULTRAVIOLET-B AND H2O2 ARE POTENT INDUCERS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION IN CULTURED KERATINOCYTES

Vascular endothelial growth factor (VEGF), also known as vascular perm eability factor, is strongly expressed by epidermal keratinocytes duri ng wound healing, in psoriasis, and in bullous diseases such as erythe ma multiforme and bullous pemphigoid. All of these disorders are chara cterized by increased microvascular permeability and angiogenesis. Sin ce the development of erythema as a result of hyperpermeable blood ves sels 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 in crease in VEGF mRNA and protein levels upon irradiation of quiescent k eratinocytes with sublethal and physiologically relevant doses of UVB. Although H2O2 was also a potent inducer of VEGF expression, the effec t of UVB irradiation is unlikely to be mediated by reactive oxygen spe cies as determined by the use of antioxidants. Further experiments rev ealed that the UVB-induced overexpression of VEGF is dependent on de n ovo 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.