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Dexamethasone inhibits interleukin-1beta-induced corneal neovascularization: role of nuclear factor-kappaB-activated stromal cells in inflammatory angiogenesis.

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)-1beta-dependent inflammatory angiogenesis is unknown. Here, we show that dexamethasone inhibits IL-1beta-induced neovascularization and the expression of the angiogenesis-related factors, vascular endothelial growth factor-A, KC, and prostaglandin E(2) in the mouse cornea 2 days after IL-1beta implantation. IL-1beta caused IkappaB-alpha phosphorylation in corneal stromal cells but not in infiltrated CD11b(+) cells 2 days after IL-1beta implantation. In contrast, both cell types were positive for phosphorylated IkappaB-alpha 4 days after IL-1beta implantation. Dexamethasone significantly inhibited IkappaB-alpha phosphorylation 2 and 4 days after IL-1beta implantation. Furthermore, dexamethasone inhibited IL-1beta-induced expression of vascular endothelial growth factor-A, KC, and prostaglandin E(2), and signaling of nuclear factor (NF)-kappaB in corneal fibroblasts in vitro. A selective NF-kappaB inhibitor attenuated IL-1beta-induced corneal angiogenesis. These findings suggest that NF-kappaB activation in the corneal stromal cells is an important early event during IL-1beta-induced corneal angiogenesis and that dexamethasone inhibits IL-1beta-induced angiogenesis partially via blocking NF-kappaB signaling.
AuthorsShintaro 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
JournalThe American journal of pathology (Am J Pathol) Vol. 171 Issue 3 Pg. 1058-65 (Sep 2007) ISSN: 0002-9440 [Print] United States
PMID17690185 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • CD11b Antigen
  • Glucocorticoids
  • Interleukin-1beta
  • NF-kappa B
  • Dexamethasone
Topics
  • Animals
  • CD11b Antigen (metabolism)
  • Cells, Cultured
  • Cornea (blood supply, cytology, physiology)
  • Corneal Neovascularization (immunology)
  • Dexamethasone (metabolism)
  • Glucocorticoids (metabolism)
  • Interleukin-1beta (metabolism)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NF-kappa B (metabolism)
  • Stromal Cells (cytology, metabolism)

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