tailieunhanh - Báo cáo y học: "CD73 represses pro-inflammatory responses in human endothelial cells"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: CD73 represses pro-inflammatory responses in human endothelial cells. | Grunewald and Ridley Journal of Inflammation 2010 7 10 http content 7 1 10 JOURNAL OF INFLAMMATION RESEARCH Open Access CD73 represses pro-inflammatory responses in human endothelial cells Jana KG Grunewald Anne J Ridley 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-a. 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-a. 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-a. Conclusions These results indicate that CD73 normally suppresses pro-inflammatory responses in human endothelial cells. Background CD73 is a 5 -ectonucleotidase that uses extracellular AMP to produce adenosine and is a GPI-anchored protein that is expressed abundantly on endothelial cells and on a subset of leukocytes 1 2 . CD73- - mice are viable but have multiple cardiovascular phenotypes 3 including cardioprotection during myocardial ischemia 4 vasoprotection 3 5 increased neointimal plaque formation and .