Abstract
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, angiopoietin (Ang)-1 and Ang2. In cultured choroidal endothelial cells we found that TNF-alpha increased Ang2 mRNA (increased transcription) and protein levels prior to those of Ang1 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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiopoietin-1 / genetics
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Angiopoietin-1 / metabolism*
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Angiopoietin-2 / genetics
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Angiopoietin-2 / metabolism*
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Blotting, Northern / methods
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Blotting, Western / methods
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Cells, Cultured
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Choroid / pathology*
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Choroidal Neovascularization / pathology
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Dactinomycin / pharmacology
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Dose-Response Relationship, Drug
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Drug Interactions
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Enzyme Activation / drug effects
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Eye / pathology
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Gene Expression / drug effects
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Gene Expression Regulation / drug effects*
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Humans
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Immunohistochemistry / methods
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Protein Synthesis Inhibitors / pharmacology
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RNA, Messenger / metabolism
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Time Factors
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / pharmacology*
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Vascular Endothelial Growth Factor A / metabolism
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Vascular Endothelial Growth Factor A / pharmacology
Substances
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Angiopoietin-1
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Angiopoietin-2
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Protein Synthesis Inhibitors
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Vascular Endothelial Growth Factor A
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Dactinomycin