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)-1 beta-dependent inflammatory angiogenesis is unknown. Here, we show that dexamethasone inhibits IL-beta-induced neovascularization and the expression of the angiogenesis-related factors, vascular endothelial growth factor-A, KC, and prostaglandin E, in the mouse cornea 2 days after IL-1 beta implantation. IL-1 beta caused I kappa B-alpha phosphorylation in corneal stromal cells but not in infiltrated CD11b(+) cells 2 days after IL-1 beta implantation. In contrast, both cell types were positive for phosphorylated I kappa B-alpha 4 days after IL-1 beta,6 implantation. Dexamethasone significantly inhibited lic&a phosphorylation 2 and 4 days after IL-1 beta implantation. Furthermore, dexamethasone inhibited IL-1 beta-induced expression of vascular endothelial growth factor-A, KC, and prostaglandin E-2, and signaling of nuclear factor (NF)-kappa B in corneal fibroblasts in vitro. A selective NF-kappa B inhibitor attenuated IL-1 beta-in- duced corneal angiogenesis. These findings suggest that NF-kappa B activation in the corneal stromal cells is an important early event during IL-1 beta-induced corneal angiogenesis and that dexamethasone inhibits IL-1 beta-induced angiogenesis partially via blocking NF-KB signaling.