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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-1α a may be an important mechanism in inflammatory angiogenesis.