title: 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.affiliation: Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Nagano
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hara
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shirakami
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kochi
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nakamura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohtaki
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsurumi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000276:immunology; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015850:Interleukin-6; D012333:RNA, Messenger
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