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Ajay Pillai, Anna Lisa Montemari, Chaunte Stampley, Curran Dalal, Folami Lamoke, Babak Baban, Manuela Bartoli; Interleukin 17 Stimulates STAT3-dependent VEGF Expression in Retinal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3547.
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Interleukin 17 (IL-17) is an inflammatory cytokine which has been shown to be involved in chronic inflammatory diseases. Our previous studies have shown that circulating (serum) levels of IL-17 are increased in diabetic patients presenting signs of macular edema and neovascularization. To better understand IL-17’s mode of action we determined its effects in inducing VEGF expression in isolated retinal endothelial cells (RECs).
RECs, of bovine and human origins, were stimulated for different times (5,15,30,60,90 minutes) with different doses (1, 10, 50, 100 ng/mL) of IL-17A or IL-17F. Other experiments were conducted by stimulating RECs with 50ng/mL of IL-17A and IL-17F for 1, 6, 12 and 24 hours. Western blotting analysis was carried out to determine activation/phosphorylation of signal transducer and activator of transcription 3 (STAT3) and protein levels of VEGF. Small interfering RNAs-induced selective blockade of STAT3 expression was also used (by transfecting RECs) to determine direct cause-effect relationship between activation of STAT3 and IL-17-induced VEGF expression.
Stimulation of RECs with both IL-17F and A resulted in a time and dose dependent effect on activation/phosphorylation of STAT3. As a result of STAT3 activation, we observed increased VEGF expression which was detectable at 6 hours and peaked at 12 hours post-treatment. Inhibition of STAT3 expression by siRNAs in RECs blunted IL-17 -induced VEGF expression.
Our results suggest that IL-17 stimulates VEGF expression in RECs. These data may explain our previous observations of up-regulation of IL-17 in diabetic patients affected by macular edema and proliferative diabetic retinopathy.
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