Activation of Adenosine A2A Receptor Attenuates Inflammatory Response in a Rat Model of Small-for-Size Liver Transplantation

Abstract

Objective To investigate the effects of adenosine A2A receptor (A2AR) activation on inflammatory responses in small-for-size liver transplantation. Materials and 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-α [TNF-α], 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-κB (NF-κB) 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-α, MIP-2, and ICAM-1 expression, reduced MIP-2 activity, inhibited IκB phosphorylation, and suppressed NF-κB activation. Conclusion Expression of A2AR is increased after transplantation, and suppresses inflammatory responses by blocking NF-κB activation in small-for-size grafts.