Correlation between augmenter of liver regeneration and IFN-γ expression in graft after rat orthotopic liver transplantation

Abstract

Background: Previous data suggested that augmenter of liver regeneration (ALR) has immunomodulation function by suppressing liver-resident NK cell activity and reducing IFN-γ expression in human liver diseases. The correlation between ALR and IFN-γ expression in graft after rat orthotopic liver transplantation remains uncertain.

Methods: A Lewis-to-BN (allograft group) and BN-to-BN (isograft group) rat liver transplantation model was used to investigate the ALR and IFN-γ expression in liver graft. Graft recipients were sacrificed at days 1, 3, 5, and 7 posttransplantation. The histopathologic changes of grafts were observed under light microscope and the intragraft expression of ALR and IFN-γ mRNA and protein was determined by real-time PCR and immunohistochemistry staining, respectively. Correlation between ALR and IFN-γ expression in graft was evaluated by Spearman rank correlation analysis.

Results: The light microscope inspection revealed severe acute rejection in the allograft group but not in the isograft group at day 7 after liver transplantation. The intragraft ALR showed slight protein expression at day 1 after liver transplantation in both groups and it was significantly increased at days 3, 5, and 7 (P < 0.05). There was no significant difference in ALR mRNA expression between the allograft group and isograft group at day 1 (1.09 ± 0.12 and 1.13 ± 0.10, respectively; P > 0.05, n = 3). The ALR mRNA level was slightly reduced at day 3 in both groups compared with that at day 1 (0.81 ± 0.11 and 0.59 ± 0.10, respectively, P > 0.05). However, it was markedly increased at day 5 (2.86 ± 0.37) and day 7 (3.19 ± 0.33) in the isograft group and was 1.57 ± 0.27 and 1.98 ± 0.13 in the allograft group at days 5 and 7, respectively. IFN-γ protein and mRNA expression in the allograft group was increased at day 1 posttransplantation and reached a peak at day 3, and then it had a slight tendency of decline at day 5 and day 7. And they in the isograft group were at a low level at all times. The levels of ALR mRNA showed a negative correlation with levels of IFN-γ mRNA in the allograft group (r = -0.86, P < 0.05, y = -0.241x + 0.586), whereas there is no correlation between ALR and IFN-γ mRNA expression in the isograft group.

Conclusion: These data revealed an obviously negative correlation between ALR and IFN-γ levels intragraft, which indicated that ALR may participate in immunoregulation of acute rejection.