Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial barrier disruption in retinal endothelial cells

Experimental Eye Research
Maria L ValleShruti Sharma

Abstract

Vascular inflammation plays a critical role in the pathogenesis of diabetic retinopathy. Recently, Interleukin-6 (IL-6) trans-signaling via soluble IL-6 receptor (sIL-6R) has emerged as a prominent regulator of inflammation in endothelial cells. This study was designed to test the hypothesis that selective inhibition of the IL-6 trans-signaling pathway will attenuate inflammation and subsequent barrier disruption in retinal endothelial cells. Human retinal endothelial cells (HRECs) were exposed to IL-6 and sIL-6R to induce IL-6 trans-signaling and the commercially available compound sgp130Fc (soluble gp-130 fused chimera) was used to selectively inhibit IL-6 trans-signaling. IL-6 trans-signaling activation caused a significant increase in STAT3 phosphorylation, expression of adhesion molecules, ROS production and apoptosis in HRECs whereas a significant decrease in mitochondrial membrane potential and NO production was observed in IL-6 trans-signaling activated cells. These changes were not observed in cells pre-treated with sgp130Fc. IL-6 trans-signaling activation was sufficient to cause barrier disruption in endothelial monolayers and pre-treatment of HRECs with sgp130Fc, maintained endothelial barrier function similar to th...Continue Reading

Citations

Jun 9, 2019·Seminars in Immunopathology·Marina MesquidaSascha Fauser
Sep 2, 2020·Investigative Ophthalmology & Visual Science·Rebekah RobinsonShruti Sharma
Nov 21, 2020·Investigative Ophthalmology & Visual Science·Felix Yemanyi, VijayKrishna Raghunathan
Jan 12, 2021·Progress in Retinal and Eye Research·Warren W PanPatrice E Fort
Dec 18, 2020·Frontiers in Physiology·Boris V ChernyakRoman A Zinovkin
Mar 12, 2021·Biochemistry. Biokhimii︠a︡·B V ChernyakR A Zinovkin
Jul 25, 2019·Biochemical and Biophysical Research Communications·Brandon A CoughlinSusanne Mohr
May 1, 2021·International Journal of Molecular Sciences·Thomas E ZapadkaPatricia R Taylor
Jun 18, 2021·JCI Insight·Nina MartinoAlejandro P Adam

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