Activation of adenosine A2A receptor attenuates inflammatory response in a rat model of small-for-size liver transplantation.
OBJECTIVE
To investigate the effects of adenosine A2A receptor (A2AR) activation on inflammatory responses in small-for-size liver transplantation.


METHODS
A rat orthotopic liver transplantation model was established using 35% grafts. Expression of A2AR in liver grafts was assessed using Western blot analysis. Recipients were given either saline solution (control group) or CGS21680 (A2AR agonist) or ZM241385 (A2AR antagonist) immediately after and 12 hours after reperfusion. Proinflammatory factors (tumor necrosis factor-alpha [TNF-alpha], macrophage inflammatory protein-2 [MIP-2], and intercellular adhesion molecule-1 [ICAM-1]) were analyzed using an enzyme-linked immunosorbent assay; neutrophil infiltration was assessed using a myeloperoxidase activity assay and hematoxylin-eosin staining; and nuclear factor-kappaB (NF-kappaB) was assessed using Western blot analysis and an electrophoretic mobility shift assay.


RESULTS
Expression of A2AR was increased after reperfusion, peaking at 6 to 12 hours after transplantation. Compared with controls, A2AR activation decreased TNF-alpha, MIP-2, and ICAM-1 expression, reduced MIP-2 activity, inhibited IkappaB phosphorylation, and suppressed NF-kappaB activation.


CONCLUSIONS
Expression of A2AR is increased after transplantation, and suppresses inflammatory responses by blocking NF-kappaB activation in small-for-size grafts.
Tang
L-M
LM
Department of General Surgery, Changzhou No. 2 Hospital, Nanjing Medical University, Nanjing, China.
Zhu
J-F
JF
Wang
F
F
Qian
J
J
Zhu
J
J
Mo
Q
Q
Lu
H-H
HH
Li
G-Q
GQ
Wang
X-H
XH
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology* / Q000201:enzymology; D016031:Liver Transplantation / Q000379:methods* / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D011917:Rats, Inbred Lew; D043705:Receptor, Adenosine A2A / Q000235:genetics* / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D054426:Chemokine CXCL2; D016207:Cytokines; D016328:NF-kappa B; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D000410:Alanine Transaminase; D000241:Adenosine