UV induces VEGF through a TNF‐α‐independent pathway

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Abstract
Vascular endothelial growth factor (VEGF) is a potent keratinocyte‐derived angiogenic factor. Prior reports suggest that following UV irradiation VEGF in keratinocytes is induced primarily by tumor necrosis factor (TNF)‐α, a cytokine synthesized and secreted by keratinocytes after UV irradiation. We investigated whether blocking TNF‐α binding to its receptors would inhibit UV‐induced VEGF expression and secretion in the keratinocyte‐derived line SCC‐12F. Irradiation with physiologic UV doses (30 mJ/cm 2 ) substantially induced VEGF mRNA in this cell line, as expected, and mRNA induction was followed by increased VEGF in medium conditioned by UV‐irradiated cells. Also as expected, TNF‐α induced VEGF expression and secretion in a dose‐dependent manner. Addition of a hexapeptide (Ac‐KWIIVW‐NH 2 ), known to block TNF‐α binding to its receptors, abrogated this TNF‐α effect on VEGF mRNA induction. However, addition of the peptide to cells immediately after UV irradiation did not substantially affect VEGF mRNA induction or secretion into the medium. Our results suggest that VEGF induction after UV irradiation is mediated by multiple mechanisms and that blocking a single pathway does not affect the response.
Funding Information
  • National Rosacea Society
  • Alexander S. Onassis Public Benefit Foundation

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