Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis.
Inflammatory mediators such as prostaglandin E2 (PGE2) and interleukin-1 (IL-1) induce angiogenesis by yet undefined mechanisms. We demonstrate that PGE2 and IL-1 induces the expression of vascular endothelial growth factor (VEGF), a selective angiogenic factor by rheumatoid synovial fibroblast cells. Transcripts for the EP1 and EP2 subtypes of PGE receptors are expressed in synovial fibroblasts. Activators of protein kinase A pathway stimulated the expression of VEGF whereas down-regulation of protein kinase C did not influence the PGE effect, suggesting that signalling from the EP2 receptor via the protein kinase A pathway is important. The induction of VEGF expression by PGE2 and interleukin-1 alpha may be an important mechanism in inflammatory angiogenesis.
Ben-Av
P
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Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, MD 20855, USA.
Crofford
L J
LJ
Wilder
R L
RL
Hla
T
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D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001427:Bacterial Toxins / Q000494:pharmacology; D001483:Base Sequence; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers; D016228:Endothelial Growth Factors / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008222:Lymphokines / Q000235:genetics*; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000209:etiology*; D011458:Prostaglandins E / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000235:genetics; D015398:Signal Transduction; D013582:Synovial Fluid / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001427:Bacterial Toxins; D017931:DNA Primers; D016228:Endothelial Growth Factors; D007375:Interleukin-1; D008222:Lymphokines; D011458:Prostaglandins E; D018078:Receptors, Prostaglandin E; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate