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

Shintaro Nakao, Yasuaki Hata, Muneki Miura, Kousuke Noda, Yusuke N. Kimura, Shuhei Kawahara, Takeshi Kita, Toshio Hisatomi, Toru Nakazawa, Yiping Jin, M. Reza Dana, Michihiko Kuwano, Mayumi Ono, Tatsuro Ishibashi, Ali Hafezi-Moghadam

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88 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1058-1065
Number of pages8
JournalAmerican Journal of Pathology
Volume171
Issue number3
DOIs
Publication statusPublished - Sep 2007

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All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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