Effects of indoleamine 2,3-dioxygenase deficiency on high-fat diet-induced hepatic inflammation.

Abstract

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, IFNγ, IL-1β, and IL-6 mRNA in the liver and the expression levels of F4/80 and TNF-α 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-β1 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.

• Authors: Junji Nagano, Masahito Shimizu, Takeshi Hara, Yohei Shirakami, Takahiro Kochi, Nobuhiko Nakamura, Hirofumi Ohtaki, Hiroyasu Ito, Takuji Tanaka, Hisashi Tsurumi, Kuniaki Saito, Mitsuru Seishima, Hisataka Moriwaki
• Journal: PloS one (PLoS One) Vol. 8 Issue 9 Pg. e73404 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24039933 (Publication Type: Journal Article)

Chemical References

• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Interleukin-6
• RNA, Messenger

Topics

• Animals
• Diet, High-Fat (adverse effects)
• Fatty Liver (etiology, genetics, immunology, pathology)
• Indoleamine-Pyrrole 2,3,-Dioxygenase (genetics, immunology)
• Inflammation (etiology, genetics, immunology, pathology)
• Interleukin-6 (genetics)
• Liver (immunology, metabolism, pathology)
• Liver Cirrhosis (etiology, genetics, immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Non-alcoholic Fatty Liver Disease
• RNA, Messenger (genetics)