Dexamethasone Inhibits Interleukin-1ß-Induced Corneal Neovascularization: Role of Nuclear Factor-B-Activated Stromal Cells in Inflammatory Angiogenesis

摘要

Dexamethasone, a synthetic corticosteroid, is widely used as a potent anti-inflammatory drug in various diseases including corneal angiogenesis. However, dexamethasone’s impact on interleukin (IL)-1ß-dependent inflammatory angiogenesis is unknown. Here, we show that dexamethasone inhibits IL-1ß-induced neovascularization and the expression of the angiogenesis-related factors, vascular endothelial growth factor-A, KC, and prostaglandin E2 in the mouse cornea 2 days after IL-1ß implantation. IL-1ß caused IB- phosphorylation in corneal stromal cells but not in infiltrated CD11b+ cells 2 days after IL-1ß implantation. In contrast, both cell types were positive for phosphorylated IB- 4 days after IL-1ß implantation. Dexamethasone significantly inhibited IB- phosphorylation 2 and 4 days after IL-1ß implantation. Furthermore, dexamethasone inhibited IL-1ß-induced expression of vascular endothelial growth factor-A, KC, and prostaglandin E2, and signaling of nuclear factor (NF)-B in corneal fibroblasts in vitro. A selective NF-B inhibitor attenuated IL-1ß-induced corneal angiogenesis. These findings suggest that NF-B activation in the corneal stromal cells is an important early event during IL-1ß-induced corneal angiogenesis and that dexamethasone inhibits IL-1ß-induced angiogenesis partially via blocking NF-B signaling.