Format

Send to

Choose Destination
PLoS One. 2014 Apr 1;9(4):e91119. doi: 10.1371/journal.pone.0091119. eCollection 2014.

Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors.

Author information

1
Department of Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
2
Department of Cardiac Pharmacology, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom; Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
3
Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
4
Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
5
MRC and Asthma UK Centre in Allergic Mechanisms of Asthma and Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
6
Pattern Recognition Receptor Discovery Performance Unit, Immuno-Inflammation Therapeutic Area, GlaxoSmithKline, Philadelphia, Pennsylvania, United States of America.
7
Department of Cardiac Pharmacology, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom.

Abstract

Human embryonic stem cell-derived endothelial cells (hESC-EC), as well as other stem cell derived endothelial cells, have a range of applications in cardiovascular research and disease treatment. Endothelial cells sense Gram-negative bacteria via the pattern recognition receptors (PRR) Toll-like receptor (TLR)-4 and nucleotide-binding oligomerisation domain-containing protein (NOD)-1. These pathways are important in terms of sensing infection, but TLR4 is also associated with vascular inflammation and atherosclerosis. Here, we have compared TLR4 and NOD1 responses in hESC-EC with those of endothelial cells derived from other stem cells and with human umbilical vein endothelial cells (HUVEC). HUVEC, endothelial cells derived from blood progenitors (blood outgrowth endothelial cells; BOEC), and from induced pluripotent stem cells all displayed both a TLR4 and NOD1 response. However, hESC-EC had no TLR4 function, but did have functional NOD1 receptors. In vivo conditioning in nude rats did not confer TLR4 expression in hESC-EC. Despite having no TLR4 function, hESC-EC sensed Gram-negative bacteria, a response that was found to be mediated by NOD1 and the associated RIP2 signalling pathways. Thus, hESC-EC are TLR4 deficient but respond to bacteria via NOD1. This data suggests that hESC-EC may be protected from unwanted TLR4-mediated vascular inflammation, thus offering a potential therapeutic advantage.

PMID:
24690886
PMCID:
PMC3972153
DOI:
10.1371/journal.pone.0091119
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center