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Inhibition of interleukin-6 trans-signaling prevents inflammation and endothelial barrier disruption in retinal endothelial cells.
- Source :
-
Experimental Eye Research . Jan2019, Vol. 178, p27-36. 10p. - Publication Year :
- 2019
-
Abstract
- 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 that of untreated cells. Thus, in conclusion, these results indicate that IL-6 trans-signaling is an important mediator of inflammation, apoptosis and barrier disruptive effects in the retinal endothelial cells and inhibition of the IL-6 trans-signaling pathway using sgp130-Fc attenuates vascular inflammation and endothelial barrier disruption. Highlights • IL-6 trans-signaling is an important mediator of inflammation and barrier disruption in the retinal endothelial cells. • An anti-inflammatory molecule, sgp130Fc selectively inhibits the IL-6 trans-signaling pathway. • sgp130Fc treatment attenuates IL-6 trans-signaling mediated inflammation and apoptosis in the retinal endothelial cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00144835
- Volume :
- 178
- Database :
- Academic Search Index
- Journal :
- Experimental Eye Research
- Publication Type :
- Academic Journal
- Accession number :
- 134422502
- Full Text :
- https://doi.org/10.1016/j.exer.2018.09.009