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(Received for publication, April 3, 1996, and in revised form, June 14, 1996)
,
From the 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.
Max-Planck-Institut für Biochemie, Am
Klopferspitz 18a, D-82152 Martinsried, Germany, the
§ Institut für Klinische Molekularbiologie und
Tumorgenetik, GSF-Forschungszentrum für Umwelt und Gesundheit,
Marchionistrasse 25, D-81377 München, Germany, and
¶ Abteilung für Molekulare Pathologie, Dermatologische
Klinik und Poliklinik der Universität München,
Frauenlobstrasse 9-11, D-80337 München, Germany
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