Absence of indoleamine 2,3-dioxygenase 2 promotes liver regeneration after partial hepatectomy in mice

The partial loss of liver due to liver transplantation or acute liver failure induces rapid liver regeneration. Recently, we reported that the selective inhibition of indoleamine 2,3-dioxygenase (Ido) 1 promotes early liver regeneration. However, the role of Ido2 in liver regeneration remains unclear. Wild-type (WT) and Ido2-deficient (Ido2-KO) mice were subjected to 70% partial hepatectomy (PHx). Hepatocyte growth was measured using immunostaining. The mRNA expression of inflammatory cytokines and production of kynurenine in intrahepatic mononuclear cells (MNCs) were analyzed using reverse transcription-quantitative PCR and high-performance liquid chromatography. The activation of NF-κB was determined by both immunocytochemistry and western blotting analysis. The ratio of liver to body weight and the frequency of proliferation cells after PHx were significantly higher in Ido2-KO mice compared with in WT mice. The expression of IL-6 and TNF-α in MNCs were transiently increased in Ido2-KO mice. The nuclear transport of NF-κB was significantly higher in peritoneal macrophages of Ido2-KO mice compared with WT mice. These results suggested that Ido2 deficiency resulted in transiently increased production of inflammatory cytokines through the activation of NF-kB, thereby promoting liver regeneration. Therefore, the regulation of Ido2 expression in MNCs may play a therapeutic role in liver regeneration under injury and disease conditions.