| First Author | Nagano J | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 9 | Pages | e73404 |
| PubMed ID | 24039933 | Mgi Jnum | J:207350 |
| Mgi Id | MGI:5556033 | Doi | 10.1371/journal.pone.0073404 |
| Citation | Nagano J, et al. (2013) Effects of indoleamine 2,3-dioxygenase deficiency on high-fat diet-induced hepatic inflammation. PLoS One 8(9):e73404 |
| abstractText | Hepatic immune regulation is associated with the progression from simple steatosis to non-alcoholic steatohepatitis, a severe condition of inflamed fatty liver. Indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme that mediates the catabolism of L-tryptophan to L-kynurenine, plays an important role in hepatic immune regulation. In the present study, we examined the effects of IDO gene silencing on high-fat diet (HFD)-induced liver inflammation and fibrosis in mice. After being fed a HFD for 26 weeks, the IDO-knockout (KO) mice showed a marked infiltration of inflammatory cells, especially macrophages and T lymphocytes, in the liver. The expression levels of F4/80, IFNgamma, IL-1beta, and IL-6 mRNA in the liver and the expression levels of F4/80 and TNF-alpha mRNA in the white adipose tissue were significantly increased in IDO-KO mice, although hepatic steatosis, the accumulation of intrahepatic triglycerides, and the amount of oxidative stress were lower than those in IDO-wild-type mice. IDO-KO mice also developed marked pericellular fibrosis in the liver, accumulated hepatic hydroxyproline, and exhibited increased expression levels of hepatic TGF-beta1 mRNA. These findings suggest that IDO-KO renders the mice more susceptible to HFD-induced hepatic inflammation and fibrosis. Therefore, IDO may have a protective effect against hepatic fibrosis, at least in this HFD-induced liver injury model. |
