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

被引:92
作者
Nakao, Shintaro
Hata, Yasuaki
Miura, Muneki
Noda, Kousuke
Kimura, Yusuke N.
Kawahara, Shulhei
Kita, Takeshi
Hisatomi, Toshio
Nakazawa, Tonu
Jin, Yiping
Dana, M. Reza
Kuwano, Michihiko
Ono, Mayumi
Ishibashi, Tatsuro
Hafezi-Moghadam, Ali
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan
[2] Kyushu Univ, Grad Sch Med Sci, Dept Med Biochem, Fukuoka 8128582, Japan
[3] Kyushu Univ, Grad Sch Med Sci, Collabo Stn 2, Fukuoka 8128582, Japan
[4] Kurume Univ, Res Ctr Innovat Canc Therapy Century 21, COE, Program Med Sci, Fukuoka, Japan
[5] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA
[6] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA
关键词
D O I
10.2353/ajpath.2007.070172
中图分类号
R36 [病理学];
学科分类号
100104 ;
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)-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.
引用
收藏
页码:1058 / 1065
页数:8
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