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

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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 chemotactic 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.

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Authors and Affiliations

  1. Department of Ophthalmology, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, 812-8582, Fukuoka, Japan

    Shigeo Yoshida, Ayako Yoshida & Tatsuro Ishibashi

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  1. Shigeo Yoshida
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  2. Ayako Yoshida
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  3. Tatsuro Ishibashi
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Correspondence to Shigeo Yoshida.

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Yoshida, S., Yoshida, A. & Ishibashi, T. Induction of IL-8, MCP-1, and bFGF by TNF-α in retinal glial cells: implications for retinal neovascularization during post-ischemic inflammation. Graefe's Arch Clin Exp Ophthalmol 242, 409–413 (2004). https://doi.org/10.1007/s00417-004-0874-2

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  • DOI: https://doi.org/10.1007/s00417-004-0874-2

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