UV induces VEGF through a TNF-alpha 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)- alpha, a cytokine synthesized and secreted by keratinocytes after UV irradiation. We investigated whether blocking TNF-alpha 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-alpha induced VEGF expression and secretion in a dose-dependent manner. Addition of a hexapeptide (Ac-KWIIVW-NH2), known to block TNF-alpha binding to its receptors, abrogated this TNF-alpha 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.
Kosmadaki
Maria G
MG
Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. mkosmada@bu.edu
Yaar
Mina
M
Arble
Bennett L
BL
Gilchrest
Barbara A
BA
D000818:Animals; D002294:Carcinoma, Squamous Cell; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D014466:Ultraviolet Rays; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010455:Peptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors