Adenosine Regulates the Proinflammatory Signaling Function of Thrombin in Endothelial Cells

The plasma level of the regulatory metabolite adenosine increases during the activation of coagulation and inflammation. Here we investigated the effect of adenosine on modulation of thrombin‐mediated proinflammatory responses in HUVECs. We found that adenosine inhibits the barrier‐disruptive effect...

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Bibliographic Details
Published in:Journal of cellular physiology Vol. 229; no. 9; pp. 1292 - 1300
Main Authors: Hassanian, Seyed Mahdi, Dinarvand, Peyman, Rezaie, Alireza R.
Format: Journal Article
Language:English
Published: United States Blackwell Publishing Ltd 01.09.2014
Wiley Subscription Services, Inc
Subjects:
Adenosine - metabolism
Adenosine - pharmacology
Adenosine A2 Receptor Agonists - metabolism
Adenosine A2 Receptor Agonists - pharmacology
Adenosine A2 Receptor Antagonists - pharmacology
Adhesion
Blood Coagulation - drug effects
Capillary Permeability
Cell Adhesion
Cells, Cultured
Coagulation
Coculture Techniques
Cyclic AMP - metabolism
Dose-Response Relationship, Drug
E-Selectin - metabolism
Enzyme Activation
Human Umbilical Vein Endothelial Cells - drug effects
Human Umbilical Vein Endothelial Cells - immunology
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Inflammation - blood
Inflammation - immunology
Inflammation - metabolism
Inflammation Mediators - metabolism
Intercellular Adhesion Molecule-1 - metabolism
Metabolites
NF-kappa B - metabolism
Protein Transport
Receptor, Adenosine A2A - genetics
Receptor, Adenosine A2A - metabolism
Receptor, Adenosine A2B - metabolism
rhoA GTP-Binding Protein - metabolism
RNA Interference
Signal Transduction - drug effects
Thrombin - metabolism
Thrombin - pharmacology
Transfection
Translocation
Vascular Cell Adhesion Molecule-1 - metabolism
ISSN:0021-9541, 1097-4652, 1097-4652
Online Access:Get full text
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Summary:The plasma level of the regulatory metabolite adenosine increases during the activation of coagulation and inflammation. Here we investigated the effect of adenosine on modulation of thrombin‐mediated proinflammatory responses in HUVECs. We found that adenosine inhibits the barrier‐disruptive effect of thrombin in HUVECs by a concentration‐dependent manner. Analysis of cell surface expression of adenosine receptors revealed that A2A and A2B are expressed at the highest level among the four receptor subtypes (A2B > A2A > A1 > A3) on HUVECs. The barrier‐protective effect of adenosine in response to thrombin was recapitulated by the A2A specific agonist, CGS 21680, and abrogated both by the siRNA knockdown of the A2A receptor and by the A2A‐specific antagonists, ZM‐241385 and SCH‐58261. The thrombin‐induced RhoA activation and its membrane translocation were both inhibited by adenosine in a cAMP‐dependent manner, providing a molecular mechanism through which adenosine exerts a barrier‐protective function. Adenosine also inhibited thrombin‐mediated activation of NF‐κB and decreased adhesion of monocytic THP‐1 cells to stimulated HUVECs via down‐regulation of expression of cell surface adhesion molecules, VCAM‐1, ICAM‐1, and E‐selectin. Moreover, adenosine inhibited thrombin‐induced elevated expression of proinflammatory cytokines, IL‐6 and HMGB‐1; and chemokines, MCP‐1, CXCL‐1, and CXCL‐3. Taken together, these results suggest that adenosine may inhibit thrombin‐mediated proinflammatory signaling responses, thereby protecting the endothelium from injury during activation of coagulation and inflammation. J. Cell. Physiol. 229: 1292–1300, 2014. © 2014 Wiley Periodicals, Inc.
Bibliography:ArticleID:JCP24568
ark:/67375/WNG-ZTN5BX59-L
National Institutes of Health - No. HL 101917; No. HL 68571
istex:5A559A70D4F4FFE6B90421C89CE2364380AE4B76
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0021-9541
1097-4652
1097-4652
DOI:10.1002/jcp.24568