Induction of IL-8, MPC-1, and bFGF by TNF-α in retinal glial cells: Implications for retinal neovascularization during post-ischemic inflammation

Shigeo Yoshida, Ayako Yoshida, Tatsuro Ishibashi

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111 Citations (Scopus)

Abstract

Background: We have demonstrated that macrophages/microglia were activated during post-ischemic inflammation in a mouse model of ischemic retinal neovascularization, and that the angiogenesis induced by tumor necrosis factor-α (TNF-α) appeared to be modulated through such angiogenic factors as interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in microvascular endothelial cells. We have extended these studies, and investigated whether TNF-α is localized in macrophages/microglia in the mouse model of retinal neovascularization, and whether TNF-α can induce angiogenic factors in retinal glial cells. Methods: C57BL/6 J pups were placed in a 75% oxygen environment on postnatal day 7 (P7) for 5 days and then returned to room air. The co-localization of TNF-α with macrophages/microglia in the ischemic retina was examined by fluorescent immunohistochemistry. Bovine retinal glial cells were isolated for Northern blot analysis to quantify the expression levels of monocyte chernotactic protein-1 (MCP-1), IL-8, bFGF, and VEGF. Results: Double staining of retinas revealed that the TNF-α expression level was enhanced in macrophages/microglia 4 days after the hypoxia. Cellular mRNA levels of MCP-1, IL-8, and bFGF, but not VEGF, were increased after treating retinal glial cells with TNF-α (100 U/ml). Conclusions: The results indicate that TNF-α is produced by activated macrophages/microglia and may participate in retinal neovascularization during post-ischemic inflammation through the induction of potent angiogenic factors in an autocrine or paracrine manner.

Original languageEnglish
Pages (from-to)409-413
Number of pages5
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume242
Issue number5
DOIs
Publication statusPublished - May 2004

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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