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Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice

PURPOSE: Increased inflammatory mediator levels are reported in diabetic retinopathy. We previously reported that β-adrenergic receptor agonists reduced inflammatory mediators in the diabetic retina; however, these agents cannot be given systemically. Here, we investigated whether Epac1 is key to th...

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Autores principales: Liu, Li, Jiang, Youde, Chahine, Adam, Curtiss, Elizabeth, Steinle, Jena J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287445/
https://www.ncbi.nlm.nih.gov/pubmed/28210097
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author Liu, Li
Jiang, Youde
Chahine, Adam
Curtiss, Elizabeth
Steinle, Jena J.
author_facet Liu, Li
Jiang, Youde
Chahine, Adam
Curtiss, Elizabeth
Steinle, Jena J.
author_sort Liu, Li
collection PubMed
description PURPOSE: Increased inflammatory mediator levels are reported in diabetic retinopathy. We previously reported that β-adrenergic receptor agonists reduced inflammatory mediators in the diabetic retina; however, these agents cannot be given systemically. Here, we investigated whether Epac1 is key to the protective effects of β-adrenergic receptor agonists. METHODS: We cultured primary human retinal endothelial cells (RECs) in normal (5 mM) or high (25 mM) glucose and treated them with an Epac1-specific agonist. Additionally, we generated Epac1 conditional vascular endothelial cell knockout mice by breeding Epac1 floxed mice with Cdh5 Cre mice to investigate the role of Epac1 in the retinal levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa beta (NFκB), and inhibitor of kappa beta (IκB). Confocal microscopy was performed to localize Epac1 in the mouse retina. RESULTS: Data showed that high glucose increased the TNF-α and IL-1β levels in the RECs, which were reduced cells treated with the Epac1 agonist. The loss of Epac1 in the retinas of the conditional knockout mice resulted in statistically significantly increased levels of TNF-α and IL-1β, as well as NFκB. CONCLUSIONS: These data indicate that Epac1 may be protective to the retina through inhibition of key inflammatory mediators.
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spelling pubmed-52874452017-02-16 Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice Liu, Li Jiang, Youde Chahine, Adam Curtiss, Elizabeth Steinle, Jena J. Mol Vis Research Article PURPOSE: Increased inflammatory mediator levels are reported in diabetic retinopathy. We previously reported that β-adrenergic receptor agonists reduced inflammatory mediators in the diabetic retina; however, these agents cannot be given systemically. Here, we investigated whether Epac1 is key to the protective effects of β-adrenergic receptor agonists. METHODS: We cultured primary human retinal endothelial cells (RECs) in normal (5 mM) or high (25 mM) glucose and treated them with an Epac1-specific agonist. Additionally, we generated Epac1 conditional vascular endothelial cell knockout mice by breeding Epac1 floxed mice with Cdh5 Cre mice to investigate the role of Epac1 in the retinal levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa beta (NFκB), and inhibitor of kappa beta (IκB). Confocal microscopy was performed to localize Epac1 in the mouse retina. RESULTS: Data showed that high glucose increased the TNF-α and IL-1β levels in the RECs, which were reduced cells treated with the Epac1 agonist. The loss of Epac1 in the retinas of the conditional knockout mice resulted in statistically significantly increased levels of TNF-α and IL-1β, as well as NFκB. CONCLUSIONS: These data indicate that Epac1 may be protective to the retina through inhibition of key inflammatory mediators. Molecular Vision 2017-01-25 /pmc/articles/PMC5287445/ /pubmed/28210097 Text en Copyright © 2017 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
Liu, Li
Jiang, Youde
Chahine, Adam
Curtiss, Elizabeth
Steinle, Jena J.
Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice
title Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice
title_full Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice
title_fullStr Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice
title_full_unstemmed Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice
title_short Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice
title_sort epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of epac1 increased inflammatory proteins in the retinal vasculature of mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287445/
https://www.ncbi.nlm.nih.gov/pubmed/28210097
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