Dexamethasone inhibits interleukin-1beta-induced corneal neovascularization: role of nuclear factor-kappaB-activated stromal cells in inflammatory angiogenesis.
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.
Nakao
Shintaro
S
Department of Ophthalmology, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
Hata
Yasuaki
Y
Miura
Muneki
M
Noda
Kousuke
K
Kimura
Yusuke N
YN
Kawahara
Shuhei
S
Kita
Takeshi
T
Hisatomi
Toshio
T
Nakazawa
Toru
T
Jin
Yiping
Y
Dana
M Reza
MR
Kuwano
Michihiko
M
Ono
Mayumi
M
Ishibashi
Tatsuro
T
Hafezi-Moghadam
Ali
A
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D003315:Cornea / Q000098:blood supply* / Q000166:cytology / Q000502:physiology; D016510:Corneal Neovascularization / Q000276:immunology*; D003907:Dexamethasone / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*
D039481:CD11b Antigen; D005938:Glucocorticoids; D053583:Interleukin-1beta; D016328:NF-kappa B; D003907:Dexamethasone
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