Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1782504158496030720 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5287445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Molecular Vision |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liuli epac1agonistdecreasedinflammatoryproteinsinretinalendothelialcellsandlossofepac1increasedinflammatoryproteinsintheretinalvasculatureofmice AT jiangyoude epac1agonistdecreasedinflammatoryproteinsinretinalendothelialcellsandlossofepac1increasedinflammatoryproteinsintheretinalvasculatureofmice AT chahineadam epac1agonistdecreasedinflammatoryproteinsinretinalendothelialcellsandlossofepac1increasedinflammatoryproteinsintheretinalvasculatureofmice AT curtisselizabeth epac1agonistdecreasedinflammatoryproteinsinretinalendothelialcellsandlossofepac1increasedinflammatoryproteinsintheretinalvasculatureofmice AT steinlejenaj epac1agonistdecreasedinflammatoryproteinsinretinalendothelialcellsandlossofepac1increasedinflammatoryproteinsintheretinalvasculatureofmice |