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

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-alpha (TNF-alpha) 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-alpha is localized in macrophages/microglia in the mouse model of retinal neovascularization, and whether TNF-alpha 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-alpha 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-alpha 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-alpha (100 U/ml).

CONCLUSIONS:

The results indicate that TNF-alpha 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.

• Authors: Shigeo Yoshida, Ayako Yoshida, Tatsuro Ishibashi
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 242 Issue 5 Pg. 409-13 (May 2004) ISSN: 0721-832X [Print] Germany
• PMID: 15029502 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL2
• Interleukin-8
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Fibroblast Growth Factor 2

Topics

• Animals
• Blotting, Northern
• Chemokine CCL2 (biosynthesis, genetics)
• Fibroblast Growth Factor 2 (biosynthesis, genetics)
• Fluorescent Antibody Technique, Indirect
• Interleukin-8 (biosynthesis, genetics)
• Macrophage Activation
• Mice
• Mice, Inbred C57BL
• Microglia (drug effects, metabolism)
• Polymerase Chain Reaction
• RNA, Messenger (metabolism)
• Reperfusion Injury (metabolism)
• Retina (drug effects, metabolism)
• Retinal Neovascularization (metabolism)
• Tumor Necrosis Factor-alpha (metabolism, pharmacology)