Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors.
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 rec...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0091119 |
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| author | Daniel M Reed Gabor Foldes Timothy Gatheral Koralia E Paschalaki Zsuzsanna Lendvai Zsolt Bagyura Tamas Nemeth Judit Skopal Bela Merkely Aurica G Telcian Leila Gogsadze Michael R Edwards Peter J Gough John Bertin Sebastian L Johnston Sian E Harding Jane A Mitchell |
| author_facet | Daniel M Reed Gabor Foldes Timothy Gatheral Koralia E Paschalaki Zsuzsanna Lendvai Zsolt Bagyura Tamas Nemeth Judit Skopal Bela Merkely Aurica G Telcian Leila Gogsadze Michael R Edwards Peter J Gough John Bertin Sebastian L Johnston Sian E Harding Jane A Mitchell |
| author_sort | Daniel M Reed |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-241a3f71d5eb429f83104ac2d430c14d |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-241a3f71d5eb429f83104ac2d430c14d2025-08-20T02:34:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9111910.1371/journal.pone.0091119Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors.Daniel M ReedGabor FoldesTimothy GatheralKoralia E PaschalakiZsuzsanna LendvaiZsolt BagyuraTamas NemethJudit SkopalBela MerkelyAurica G TelcianLeila GogsadzeMichael R EdwardsPeter J GoughJohn BertinSebastian L JohnstonSian E HardingJane A MitchellHuman 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.https://doi.org/10.1371/journal.pone.0091119 |
| spellingShingle | Daniel M Reed Gabor Foldes Timothy Gatheral Koralia E Paschalaki Zsuzsanna Lendvai Zsolt Bagyura Tamas Nemeth Judit Skopal Bela Merkely Aurica G Telcian Leila Gogsadze Michael R Edwards Peter J Gough John Bertin Sebastian L Johnston Sian E Harding Jane A Mitchell Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors. PLoS ONE |
| title | Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors. |
| title_full | Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors. |
| title_fullStr | Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors. |
| title_full_unstemmed | Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors. |
| title_short | Pathogen sensing pathways in human embryonic stem cell derived-endothelial cells: role of NOD1 receptors. |
| title_sort | pathogen sensing pathways in human embryonic stem cell derived endothelial cells role of nod1 receptors |
| url | https://doi.org/10.1371/journal.pone.0091119 |
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