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 signifi- cantly 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.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Cancer Research