Dexamethasone inhibits interleukin-1β-induced corneal neovascularization: Role of nuclear factor-κB-activated stromal cells in inflammatory angiogenesis

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)-1β-dependent inflammatory angiogenesis is unknown. Here, we show that dexamethasone inhibits IL-1β-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-1β implantation. IL-1β caused IκB-α phosphorylation in corneal stromal cells but not in infiltrated CD11b⁺ cells 2 days after IL-1β implantation. In contrast, both cell types were positive for phosphorylated IκB-α 4 days after IL-1β implantation. Dexamethasone significantly inhibited IκB-α phosphorylation 2 and 4 days after IL-1β implantation. Furthermore, dexamethasone inhibited IL-1β-induced expression of vascular endothelial growth factor-A, KC, and prostaglandin E₂, and signaling of nuclear factor (NF)-κB in corneal fibroblasts in vitro. A selective NF-κB inhibitor attenuated IL-1β-induced corneal angiogenesis. These findings suggest that NF-κB activation in the corneal stromal cells is an important early event during IL-1β-induced corneal angiogenesis and that dexamethasone inhibits IL-1β-induced angiogenesis partially via blocking NF-κB signaling.