Role of IL-6 in Angiotensin-Induced Expression of VEGF in the Mouse Retina

Abstract

Purpose:: To investigate the role of the inflammatory cytokine IL-6 in Angiotensin II (Ang II)-induced increases in VEGF expression and retinal vascular pathology. Production of pro-inflammatory cytokines has been shown to play a critical role in a wide variety of ischemic retinal vascular diseases. Ang II and the angiogenic growth factor VEGF have been implicated in both the initiation of retinal vascular inflammation and development of retinal vascular disease. However, the detailed mechanisms of this process and the potential interactions between the actions of inflammatory agonists and Ang II in promoting the expression of VEGF are poorly understood.

Methods:: Wild-type c57BL6 mice and IL-6-deficient mice were implanted subcutaneously with osmotic minipumps to deliver Ang II for 2 weeks (5mg/Kg/day). Age-matched wild type and IL-6 knock-out mice served as controls. Western blotting analysis was performed to measure VEGF protein levels. Frozen retinal sections were reacted with Griffonia Simplicifolia isolectin B4 to label the retinal vessels and processed for morphometric analysis of retinal vascular density.

Results:: Infusion of wild-type mice with Ang II stimulated a 238% increase in VEGF protein levels vs control which was associated with a 116% increase in retinal vascular density. Knocking out IL-6 blocked the Ang II-induced increase in VEGF protein and prevented the increase in retinal vascular density.

Conclusions:: These results indicate that IL-6 expression is required for Ang-II-induced over-expression of VEGF and retinal vascular density increases. These data imply a critical role for IL-6 in mediating Ang II’s pathological effects in causing vascular inflammation during retinopathy.

Keywords: neovascularization • inflammation • gene/expression