Cyclooxygenase 2 is a key enzyme for inflammatory cytokine induced angiogenesis

Abstract

Abstract: : Purpose: To investigate the role of Cyclooxygenase 2 (COX2) and some prostanoids in an inflammatory cytokine, IL–1ß–induced angiogenesis. Methods: Human umbilical vein endothelial cells (HUVECs) were used for in vitro experiments. COX2 expression in HUVEC was analyzed by western blotting. HUVECs migration were analyzed by Boyden chamber assay. We analyzed in vivo angiogenesis by mouse corneal pocket assay. The concentrations of prostaglandin E2 (PGE2) and thromboxane A2/ thromboxane B2 (TXA2/TXB2) in the condition medium of HUVECs were measured using commercially available ELISA kits. Results: IL–1ß enhanced expression of various prostanoids and this expression was blocked by COX2 selective inhibitors. IL–1ß markedly induced angiogenesis in vitro and in vivo, which were significantly inhibited by COX2 selective inhibitors, but not by a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor. EP2, EP4 (prostaglandin E2 receptors) agonists and thromboxane A2 (TXA2) receptor agonists induced angiogenesis in vitro and in vivo, and IL–1ß–induced angiogenesis was blocked by an EP4 antagonist and a TXA2 receptor antagonist. IL–1ß induced much less angiogenesis in cornea of COX2 knockout mice than that of wild type mice. Conclusions: COX2 and some prostanoids play a key role in IL–1ß–induced angiogenesis.

Keywords: neovascularization • cornea: basic science • inflammation