Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Arthritis, Rheumatoid / metabolism*
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Bacterial Toxins / pharmacology
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Base Sequence
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Colforsin / pharmacology
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Cyclic AMP-Dependent Protein Kinases / metabolism
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DNA Primers
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Endothelial Growth Factors / genetics*
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Fibroblasts / metabolism
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Gene Expression Regulation*
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Humans
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Interleukin-1 / pharmacology*
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Lymphokines / genetics*
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Molecular Sequence Data
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Neovascularization, Pathologic / etiology*
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Prostaglandins E / pharmacology*
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Protein Kinase C / metabolism
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Receptors, Prostaglandin E / genetics
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Signal Transduction
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Synovial Fluid / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Bacterial Toxins
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DNA Primers
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Endothelial Growth Factors
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Interleukin-1
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Lymphokines
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Prostaglandins E
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Receptors, Prostaglandin E
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Colforsin
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Tetradecanoylphorbol Acetate