Pathogen Sensing Pathways in Human Embryonic Stem Cell Derived-Endothelial Cells: Role of NOD1 Receptors

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2014