Role of NF-κb-mediated interleukin-8 expression in intraocular neovascularization

Ayako Yoshida, Shigeo Yoshida, Abmad K. Khalil, Tatsuro Ishibashi, Hajime Inomata

研究成果: Contribution to journalArticle査読

113 被引用数 (Scopus)

抄録

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-κB activation was evaluated by immunoblot analysis and by electrophoretic mobility shift assay, and IL-8 anti 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-κB activation and increased IL-8 and VEGF mRNA. Furthermore, pyrrolidine dithiocarbamate, a specific inhibitor of NF-κB 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-κB may contribute to the pathogenesis of intraocular neovascularization.

本文言語英語
ページ(範囲)1097-1106
ページ数10
ジャーナルInvestigative Ophthalmology and Visual Science
39
7
出版ステータス出版済み - 6 1 1998

All Science Journal Classification (ASJC) codes

  • 眼科学
  • 感覚系
  • 細胞および分子神経科学

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