Research

CD73 represses pro-inflammatory responses in human endothelial cells

Jana KG Grünewald and Anne J Ridley

King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London SE1 1UL, UK

author email corresponding author email

Journal of Inflammation 2010, 7:10doi:10.1186/1476-9255-7-10

Published:	5 February 2010

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-α. 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-α. 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-α.

Conclusions

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