Augmenter of liver regeneration attenuates acute rejection after rat liver transplantation

BACKGROUND: The role of augmenter of liver regeneration (ALR) on liver transplantation immune regulation remains unknown. METHODS: Male Lewis and Brown-Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100 mu g/kg/d, intramuscular injection postoperatively). Rats were sacrificed at indicated times for assessment of cytokines production, T-cell (TC) activation and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of H-3-thymidine TCs. RESULTS: (1) Treatment with ALR significantly decreased interleukin-2 and interferon-gamma expression, promoted TC apoptosis, and prolonged the survival of allografts; (2) KCs in ALR group and isograft group that had significantly increased interleukin-10 and decreased tumor necrosis factor-alpha expression were able to inhibit TC proliferation and induce their apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly inhibited TC proliferation and activation and induced TC apoptosis. CONCLUSIONS: ALR could inhibit TC proliferation and function both in vivo and in vitro and attenuate acute rejection after liver transplantation. (C) 2016 Elsevier Inc. All rights reserved.