UV induces VEGF through a TNF‐α‐independent pathway

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...

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Bibliographic Details
Published in:The FASEB journal 2003-03, Vol.17 (3), p.1-17
Main Authors: Kosmadaki, Maria G., Yaar, Mina, Arble, Bennett L., Gilchrest, Barbara A.
Format: Article
Language:English
Subjects:
angiogenesis
Animals
Carcinoma, Squamous Cell
cytokines
Endothelial Growth Factors - biosynthesis
Endothelial Growth Factors - genetics
Gene Expression Regulation
Intercellular Signaling Peptides and Proteins - biosynthesis
Intercellular Signaling Peptides and Proteins - genetics
Lymphokines - biosynthesis
Lymphokines - genetics
Models, Biological
Peptides - pharmacology
RNA, Messenger - biosynthesis
Signal Transduction
skin
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor Necrosis Factor-alpha - physiology
Ultraviolet Rays
Up-Regulation
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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Summary: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/cm2) 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‐NH2), 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.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.02-0379fje