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.
|
Authors | 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 |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 171
Issue 3
Pg. 1058-65
(Sep 2007)
ISSN: 0002-9440 [Print] United States |
PMID | 17690185
(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)
|