Epac1 Blocks NLRP3 Inflammasome to Reduce IL-1β in Retinal Endothelial Cells and Mouse Retinal Vasculature
Joint Authors
Steinle, Jena J.
Jiang, Youde
Liu, Li
Curtiss, Elizabeth
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-02-28
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
Inflammation is an important component of diabetic retinal damage.
We previously reported that a novel β-adrenergic receptor agonist, Compound 49b, reduced Toll-like receptor 4 (TLR4) signaling in retinal endothelial cells (REC) grown in high glucose.
Others reported that TLR4 activates high-mobility group box 1 (HMGB1), which has been associated with the NOD-like receptor 3 (NLRP3) inflammasome.
Thus, we hypothesized that Epac1, a downstream mediator of β-adrenergic receptors, would block TLR4/HMGB1-mediated stimulation of the NLRP3 inflammasome, leading to reduced cleavage of caspase-1 and interleukin-1 beta (IL-1β).
We generated vascular specific conditional knockout mice for Epac1 and used REC grown in normal and high glucose treated with an Epac1 agonist and/or NLRP3 siRNA.
Protein analyses were done for Epac1, TLR4, HMGB1, NLRP3, cleaved caspase-1, and IL-1β.
Loss of Epac1 in the mouse retinal vasculature significantly increased all of the inflammatory proteins.
Epac1 effectively reduced high glucose-induced increases in TLR4, HMGB1, cleaved caspase-1, and IL-1β in REC.
Taken together, the data suggest that Epac1 reduces formation of the NLRP3 inflammasome to reduce inflammatory responses in the retinal vasculature.
American Psychological Association (APA)
Jiang, Youde& Liu, Li& Curtiss, Elizabeth& Steinle, Jena J.. 2017. Epac1 Blocks NLRP3 Inflammasome to Reduce IL-1β in Retinal Endothelial Cells and Mouse Retinal Vasculature. Mediators of Inflammation،Vol. 2017, no. 2017, pp.1-7.
https://search.emarefa.net/detail/BIM-1188196
Modern Language Association (MLA)
Jiang, Youde…[et al.]. Epac1 Blocks NLRP3 Inflammasome to Reduce IL-1β in Retinal Endothelial Cells and Mouse Retinal Vasculature. Mediators of Inflammation No. 2017 (2017), pp.1-7.
https://search.emarefa.net/detail/BIM-1188196
American Medical Association (AMA)
Jiang, Youde& Liu, Li& Curtiss, Elizabeth& Steinle, Jena J.. Epac1 Blocks NLRP3 Inflammasome to Reduce IL-1β in Retinal Endothelial Cells and Mouse Retinal Vasculature. Mediators of Inflammation. 2017. Vol. 2017, no. 2017, pp.1-7.
https://search.emarefa.net/detail/BIM-1188196
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1188196