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
相关论文
共 42 条
  • [11] Detection of interleukin-1 beta in the tear fluid of patients with corneal disease with or without conjunctival involvement
    Fukuda, M
    Mishima, H
    Otori, T
    [J]. JAPANESE JOURNAL OF OPHTHALMOLOGY, 1997, 41 (02) : 63 - 66
  • [12] Gendron RL, 2001, MOL VIS, V7, P107
  • [13] INHIBITION OF TUMOR-GROWTH, VASCULARIZATION, AND COLLAGENOLYSIS IN THE RABBIT CORNEA BY MEDROXYPROGESTERONE
    GROSS, J
    AZIZKHAN, RG
    BISWAS, C
    BRUNS, RR
    HSIEH, DST
    FOLKMAN, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (02): : 1176 - 1180
  • [14] Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase
    Hafezi-Moghadam, A
    Simoncini, T
    Yang, ZQ
    Limbourg, FP
    Plumier, JC
    Rebsamen, MC
    Hsieh, CM
    Chui, DS
    Thomas, KL
    Prorock, AJ
    Laubach, VE
    Moskowitz, MA
    French, BA
    Ley, K
    Liao, JK
    [J]. NATURE MEDICINE, 2002, 8 (05) : 473 - 479
  • [15] Hong JW, 2001, INVEST OPHTH VIS SCI, V42, P2795
  • [16] ISHIBASHI T, 1985, ARCH OPHTHALMOL-CHIC, V103, P708
  • [17] Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis
    Kuwano, T
    Nakao, S
    Yamamoto, H
    Tsuneyoshi, M
    Yamamoto, T
    Kuwano, M
    Ono, M
    [J]. FASEB JOURNAL, 2004, 18 (02) : 300 - 310
  • [18] EVALUATION OF DEXAMETHASONE ACETATE AS A TOPICAL OPHTHALMIC FORMULATION
    LEIBOWITZ, HM
    KUPFERMAN, A
    STEWART, RH
    KIMBROUGH, RL
    [J]. AMERICAN JOURNAL OF OPHTHALMOLOGY, 1978, 86 (03) : 418 - 423
  • [19] GLUCOCORTICOID INFLUENCE ON GROWTH OF VASCULAR WALL CELLS IN CULTURE
    LONGENECKER, JP
    KILTY, LA
    JOHNSON, LK
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 1982, 113 (02) : 197 - 202
  • [20] Transcriptional regulation of vascular endothelial growth factor in cancer
    Loureiro, RMB
    D'Amore, PA
    [J]. CYTOKINE & GROWTH FACTOR REVIEWS, 2005, 16 (01) : 77 - 89