Dexamethasone inhibits interleukin-1β-induced corneal neovascularization -: Role of nuclear factor-κB-activated stromal cells in inflammatory angiogenesis
Dexamethasone inhibits interleukin-1β-induced corneal neovascularization -: Role of nuclear factor-κB-activated stromal cells in inflammatory angiogenesis
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DOI：
10.2353/ajpath.2007.070172
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发表时间：
2007-09-01
影响因子：
6
通讯作者：
Hafezi-Moghadam, Ali
中科院分区：
文献类型：
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作者：
Nakao, Shintaro;Hata, Yasuaki;Hafezi-Moghadam, Ali
地塞米松是一种合成皮质类固醇，作为有效的抗炎药广泛用于治疗包括角膜血管生成在内的各种疾病。然而，地塞米松对白细胞介素 (IL)-1 β 依赖性炎症血管生成的影响尚不清楚。在这里，我们发现在IL-1β植入后2天，地塞米松抑制小鼠角膜中IL-β诱导的新生血管形成以及血管生成相关因子、血管内皮生长因子-A、KC和前列腺素E的表达。 IL-1β植入2天后，IL-1β引起角膜基质细胞中的IκB-α磷酸化，但不引起浸润的CD11b(+)细胞中的IκB-α磷酸化。相反，在 IL-1 beta,6 植入后 4 天，两种细胞类型均呈磷酸化 I kappa B-alpha 阳性。 IL-1β植入后2天和4天，地塞米松显着抑制lic&a磷酸化。此外，地塞米松在体外抑制角膜成纤维细胞中 IL-1β 诱导的血管内皮生长因子 A、KC 和前列腺素 E-2 的表达以及核因子 (NF)-κ B 的信号传导。选择性 NF-κ B 抑制剂可减弱 IL-1 β 诱导的角膜血管生成。这些发现表明，角膜基质细胞中的 NF-κB 激活是 IL-1β 诱导的角膜血管生成过程中的一个重要早期事件，并且地塞米松部分通过阻断 NF-κB 信号传导来抑制 IL-1β 诱导的血管生成。
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.