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.

Inhibition of hypoxia inducible factor by phenethyl isothiocyanate

“…ROS generally promote activation of HIF [41][42][43][44][45][46][47] and consistent with this, we demonstrated that NAC and catalase decreased induction of HIF activity in hypoxic conditions. However, only NAC, which contains a free thiol, reversed the ability of PEITC to inhibit HIF activity, whereas the non-thiol based antioxidants catalase and Trolox either had no effect, or enhanced the inhibitory effects of PEITC.…”

“…Treatment of cells with hydrogen peroxide is sufficient to stabilise HIF1α and induce expression of HIF target genes, even in normoxia [41]. Moreover, HIF activation in normoxia and hypoxia is inhibited by antioxidants such as GSH, its metabolic precursor N- …”

Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation

“…H 2 O 2 increased VEGF expression in keratinocytes [37] and in endothelial cells [38]. We have previously shown that psoriasin is induced by stress stimuli such as ROS [13].…”

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

“…Expression of VEGF is known to be regulated by other mediators, including platelet-derived growth factor (35), TGF-␤ (36), IL-1 (28), oxygen radicals and nitric oxide (30,(37)(38)(39), and hypoxia (32,38,40). The synovium is chronically hypoxic in RA and probably also in CIA: biochemical evidence of anaerobic metabolism suggests that blood flow is insufficient to meet the high metabolic demands of inflamed synovial tissue (41).…”