Document Detail

Role of NF-kappaB-mediated interleukin-8 expression in intraocular neovascularization.
MedLine Citation:
PMID:  9620068     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To investigate the role of interleukin (IL)-8 in intraocular neovascularization and the mechanism of its production. METHODS: Interleukin-8 was measured with enzyme-linked immunosorbent assays in vitreous and aqueous fluid obtained from patients with neovascular diseases. Localization of IL-8 was examined by immunohistochemistry. An in vitro angiogenesis assay was performed on collagen gels, by using bovine aortic endothelial cells to determine the effect of the vitreous fluid. In bovine retinal glial cells under hypoxia, NF-kappaB activation was evaluated by immunoblot analysis and by electrophoretic mobility shift assay, and IL-8 and vascular endothelial growth factor (VEGF) mRNA expression was determined by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: The concentration of IL-8 in vitreous fluid of patients with retinal neovascularization was significantly higher than that of patients without neovascular disease. Interleukin-8 immunostaining was detected in vascular endothelial cells and glial cells in the retinas with neovascularization. Vitreous fluid with high concentrations of IL-8 induced tubular morphogenesis in endothelial cells, and this effect was inhibited to a similar extent by neutralizing antibodies to IL-8 or to VEGF. In glial cells, in vitro, hypoxia induced NF-kappaB activation and increased IL-8 and VEGF mRNA. Furthermore, pyrrolidine dithiocarbamate, a specific inhibitor of NF-kappaB activation, prevented the induction of the IL-8 gene, but not that of the VEGF gene. CONCLUSIONS: These results suggest that IL-8 induced by hypoxia and mediated by NF-kappaB may contribute to the pathogenesis of intraocular neovascularization.
A Yoshida; S Yoshida; A K Khalil; T Ishibashi; H Inomata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  39     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1998-06-11     Completed Date:  1998-06-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1097-106     Citation Subset:  IM    
Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Anoxia / complications
Aqueous Humor / metabolism
Cells, Cultured
DNA Primers / chemistry
Endothelial Growth Factors / genetics,  metabolism
Endothelium, Vascular / metabolism,  pathology
Enzyme-Linked Immunosorbent Assay
Immunoenzyme Techniques
Interleukin-8 / genetics,  metabolism*
Lymphokines / genetics,  metabolism
NF-kappa B / antagonists & inhibitors,  physiology*
Neuroglia / metabolism
Polymerase Chain Reaction
Pyrrolidines / pharmacology
RNA, Messenger / metabolism
Retinal Neovascularization / etiology,  metabolism*,  pathology
Thiocarbamates / pharmacology
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Vitreous Body / metabolism
Reg. No./Substance:
0/DNA Primers; 0/Endothelial Growth Factors; 0/Interleukin-8; 0/Lymphokines; 0/NF-kappa B; 0/Pyrrolidines; 0/RNA, Messenger; 0/Thiocarbamates; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 25769-03-3/pyrrolidine dithiocarbamic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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