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J Inflamm (Lond). 2010 Feb 5;7(1):10. doi: 10.1186/1476-9255-7-10.

CD73 represses pro-inflammatory responses in human endothelial cells.

Author information

1
King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London SE1 1UL, UK. anne.ridley@kcl.ac.uk.

Abstract

BACKGROUND:

CD73 is a 5'-ectonucleotidase that produces extracellular adenosine, which then acts on G protein-coupled purigenic receptors to induce cellular responses. CD73 has been reported to regulate expression of pro-inflammatory molecules in mouse endothelium. Our aim is to determine the function of CD73 in human endothelial cells.

METHODS:

We used RNAi to deplete CD73 levels in human umbilical cord endothelial cells (HUVECs).

RESULTS:

CD73 depletion resulted in a strong reduction in adenosine production, indicating that CD73 is the major source of extracellular adenosine in HUVECs. We find that CD73 depletion induces a similar response to pro-inflammatory stimuli such as the cytokine TNF-alpha. In CD73-depleted cells, surface levels of the leukocyte adhesion molecules ICAM-1, VCAM-1 and E-selectin increase. This correlates with increased translocation of the transcription factor NF-kB to the nucleus, which is known to regulate ICAM-1, VCAM-1 and E-selectin expression in response to TNF-alpha. Adhesion of monocytic cells to endothelial cells is enhanced. In addition, CD73-depleted cells become elongated, have higher levels of stress fibres and increased endothelial permeability, resembling known responses to TNF-alpha.

CONCLUSIONS:

These results indicate that CD73 normally suppresses pro-inflammatory responses in human endothelial cells.

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