CD73 represses pro-inflammatory responses in human endothelial cells

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 C...

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Bibliographic Details
Published in:Journal of inflammation (London, England) England), 2010-02, Vol.7 (1), p.10-10
Main Authors: Grünewald, Jana Kg, Ridley, Anne J
Format: Article
Language:English
Subjects:
Cells
Diagnosis
Endothelium
Flow cytometry
Genetic aspects
Genotype & phenotype
Hypoxia
Immune response
Inflammation
Leukocytes
Lymphocytes
Medical research
Nucleotidases
Permeability
Properties
Tumor necrosis factor
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Summary: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. We used RNAi to deplete CD73 levels in human umbilical cord endothelial cells (HUVECs). 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. These results indicate that CD73 normally suppresses pro-inflammatory responses in human endothelial cells.
ISSN:1476-9255
1476-9255
DOI:10.1186/1476-9255-7-10