MicroRNA-146 Inhibits Thrombin-Induced NF-κB Activation and Subsequent Inflammatory Responses in Human Retinal Endothelial Cells

2014 ◽  
Vol 55 (8) ◽  
pp. 4944 ◽  
Author(s):  
Colleen Cowan ◽  
Chithra K. Muraleedharan ◽  
James J. O'Donnell ◽  
Pawan K. Singh ◽  
Hazel Lum ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Retinal Endothelial Cells

scholarly journals Epac1 Blocks NLRP3 Inflammasome to Reduce IL-1βin Retinal Endothelial Cells and Mouse Retinal Vasculature

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Youde Jiang ◽  
Li Liu ◽  
Elizabeth Curtiss ◽  
Jena J. Steinle
Keyword(s):  
Endothelial Cells ◽  
Nlrp3 Inflammasome ◽  
High Glucose ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
High Mobility ◽  
Conditional Knockout ◽  
Retinal Vasculature ◽  
Retinal Endothelial Cells ◽  
Caspase 1

Inflammation is an important component of diabetic retinal damage. We previously reported that a novelβ-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 ofβ-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-1βin REC. Taken together, the data suggest that Epac1 reduces formation of the NLRP3 inflammasome to reduce inflammatory responses in the retinal vasculature.

scholarly journals Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR/Cas9-Corrected Mutation

2021 ◽  
Vol 22 (5) ◽  
pp. 2381
Author(s):  
Hui-Yung Song ◽  
Yi-Ping Yang ◽  
Yueh Chien ◽  
Wei-Yi Lai ◽  
Yi-Ying Lin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Late Onset ◽  
Critical Role ◽  
Vascular Complications ◽  
Digital Pcr ◽  
Mapk Signaling ◽  
Autophagic Flux ◽  
Fabry Patient ◽  
Genomic Editing

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.

scholarly journals The ATP Receptors P2X7 and P2X4 Modulate High Glucose and Palmitate-Induced Inflammatory Responses in Endothelial Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0125111 ◽  
Author(s):  
Ramasri Sathanoori ◽  
Karl Swärd ◽  
Björn Olde ◽  
David Erlinge
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Inflammatory Responses ◽  
Atp Receptors

scholarly journals Regulatory T Cells Protect Fine Particulate Matter-Induced Inflammatory Responses in Human Umbilical Vein Endothelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Wen-cai Zhang ◽  
Yan-ge Wang ◽  
Zheng-feng Zhu ◽  
Fang-qin Wu ◽  
Yu-dong Peng ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Particulate Matter ◽  
Inflammatory Cytokines ◽  
Fine Particles ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Fine Particulate Matter ◽  
Fine Particulate ◽  
Umbilical Vein Endothelial Cells

Objective. To investigate the role of CD4+CD25+T cells (Tregs) in protecting fine particulate matter (PM-) induced inflammatory responses, and its potential mechanisms.Methods. Human umbilical vein endothelial cells (HUVECs) were treated with graded concentrations (2, 5, 10, 20, and 40 µg/cm2) of suspension of fine particles for 24h. For coculture experiment, HUVECs were incubated alone, with CD4+CD25−T cells (Teff), or with Tregs in the presence of anti-CD3 monoclonal antibodies for 48 hours, and then were stimulated with or without suspension of fine particles for 24 hours. The expression of adhesion molecules and inflammatory cytokines was examined.Results. Adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and inflammatory cytokines, such as interleukin (IL-) 6 and IL-8, were increased in a concentration-dependent manner. Moreover, the adhesion of human acute monocytic leukemia cells (THP-1) to endothelial cells was increased and NF-κB activity was upregulated in HUVECs after treatment with fine particles. However, after Tregs treatment, fine particles-induced inflammatory responses and NF-κB activation were significantly alleviated. Transwell experiments showed that Treg-mediated suppression of HUVECs inflammatory responses impaired by fine particles required cell contact and soluble factors.Conclusions. Tregs could attenuate fine particles-induced inflammatory responses and NF-κB activation in HUVECs.

scholarly journals Enhanced n-3 phospholipid content reduces inflammatory responses in bovine endothelial cells

2012 ◽  
Vol 95 (12) ◽  
pp. 7137-7150 ◽  
Author(s):  
G.A. Contreras ◽  
S.A. Mattmiller ◽  
W. Raphael ◽  
J.C. Gandy ◽  
L.M. Sordillo
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Phospholipid Content ◽  
Bovine Endothelial Cells

scholarly journals The quinic acid derivative KZ-41 prevents glucose-induced caspase-3 activation in retinal endothelial cells through an IGF-1 receptor dependent mechanism

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0180808 ◽  
Author(s):  
Hui He ◽  
Rebecca L. Weir ◽  
Jordan J. Toutounchian ◽  
Jayaprakash Pagadala ◽  
Jena J. Steinle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Acid Derivative ◽  
Caspase 3 ◽  
Quinic Acid ◽  
Retinal Endothelial Cells ◽  
Dependent Mechanism
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