Sequential induction of angiogenic growth factors by TNF-α in choroidal endothelial cells

被引:46
作者
Hangai, M
He, SK
Hoffmann, S
Lim, JI
Ryan, SJ
Hinton, DR [1 ]
机构
[1] Univ So Calif, Dept Ophthalmol, Doheny Eye Inst, Keck Sch Med, Los Angeles, CA 90089 USA
[2] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Dept Pathol, Los Angeles, CA USA
[3] Univ So Calif, Keck Sch Med, Beckman Macular Res Ctr, Doheny Eye Inst, Los Angeles, CA USA
关键词
angiogenesis; choriocapillaris; cytokine; growth factors; gene expression;
D O I
10.1016/j.jneuroim.2005.09.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Inflammatory mediators have been proposed to play a critical role in the pathogenesis of choroidal neovascularization, a blinding complication of age-related macular degeneration. We evaluated the expression of TNF-alpha in human choroidal neovascular membranes and found that it colocalized with cells expressing VEGF, angiopoictin (Ang)-l and Ang2. In cultured choroidal endothelial cells we found that TNF-alpha increased Ang2 mRNA (increased transcription) and protein levels prior to those of Ang] and VEGF. The results raise the possibility that during neovascularization, TNF-alpha may modulate endothelial plasticity and survival by sequential inactivation of Tie2 followed by activation of Tie2 and VEGF receptors. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:45 / 56
页数:12
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