Next Article in Journal / Special Issue
Diabetic Retinopathy Screening Programme: Attendance, Barriers and Enablers amongst Young People with Diabetes Mellitus Aged 12–26 Years
Previous Article in Journal
Crosstalk of Endothelial and Mesenchymal Stromal Cells under Tissue-Related O2
Previous Article in Special Issue
Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells
Article

Interleukin-6 Trans-Signaling Mediated Regulation of Paracellular Permeability in Human Retinal Endothelial Cells

1
Center for Biotechnology & Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
2
Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
3
Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
4
Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Winfried M. Amoaku
Int. J. Transl. Med. 2021, 1(2), 137-153; https://doi.org/10.3390/ijtm1020010
Received: 29 June 2021 / Revised: 1 September 2021 / Accepted: 7 September 2021 / Published: 16 September 2021
(This article belongs to the Special Issue Diabetic Retinopathy)
Long-term hyperglycemia-mediated oxidative stress and inflammation lead to the blood-retinal barrier (BRB) dysfunction and increased vascular permeability associated with diabetic retinopathy (DR). Interleukin-6 (IL-6) is one of the primary mediators of retinal vascular inflammation. IL-6 signaling through its membrane-bound IL-6 receptor is known as classical signaling, and through a soluble IL-6 receptor (sIL-6R) is known as trans-signaling. Increasing evidence suggests that classical signaling is primarily anti-inflammatory, whereas trans-signaling induces the pro-inflammatory effects of IL-6. The purpose of this study was to compare the effects of these two pathways on paracellular permeability and expression of genes involved in inter-endothelial junctions in human retinal endothelial cells (HRECs). IL-6 trans-signaling activation caused significant disruption to paracellular integrity, with increased paracellular permeability, and was associated with significant changes in gene expression related to adherens, tight, and gap junctions. IL-6 classical signaling did not alter paracellular resistance in HRECs and had no distinct effects on gene expression. In conclusion, IL-6 trans-signaling, but not classical signaling, is a major mediator of the increased paracellular permeability characteristic of inner BRB breakdown in diabetic retinopathy. This study also identified potential inter-endothelial junction genes involved in the IL-6 trans-signaling mediated regulation of paracellular permeability in HRECs. View Full-Text
Keywords: RNA-Seq; diabetic retinopathy; paracellular permeability; gene expression; IL-6 trans-signaling; retinal endothelial cells RNA-Seq; diabetic retinopathy; paracellular permeability; gene expression; IL-6 trans-signaling; retinal endothelial cells
Show Figures

Figure 1

MDPI and ACS Style

Glass, J.; Robinson, R.; Lee, T.-J.; Sharma, A.; Sharma, S. Interleukin-6 Trans-Signaling Mediated Regulation of Paracellular Permeability in Human Retinal Endothelial Cells. Int. J. Transl. Med. 2021, 1, 137-153. https://doi.org/10.3390/ijtm1020010

AMA Style

Glass J, Robinson R, Lee T-J, Sharma A, Sharma S. Interleukin-6 Trans-Signaling Mediated Regulation of Paracellular Permeability in Human Retinal Endothelial Cells. International Journal of Translational Medicine. 2021; 1(2):137-153. https://doi.org/10.3390/ijtm1020010

Chicago/Turabian Style

Glass, Joshua, Rebekah Robinson, Tae-Jin Lee, Ashok Sharma, and Shruti Sharma. 2021. "Interleukin-6 Trans-Signaling Mediated Regulation of Paracellular Permeability in Human Retinal Endothelial Cells" International Journal of Translational Medicine 1, no. 2: 137-153. https://doi.org/10.3390/ijtm1020010

Find Other Styles

Article Access Map by Country/Region

1
Back to TopTop