title: Ability of IDO to attenuate liver injury in alpha-galactosylceramide-induced hepatitis model.
abstract: IDO converts tryptophan to l-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, we examined the effect of IDO in α-galactosylceramide (α-GalCer)-induced hepatitis. The increase in IDO expression in the liver of wild-type (WT) mice administered α-GalCer was confirmed by real-time PCR, Western blotting, and IDO immunohistochemical analysis. The serum alanine aminotransferase levels in IDO-knockout (KO) mice after α-GalCer injection significantly increased compared with those in WT mice. 1-Methyl-D-tryptophan also exacerbated liver injury in this murine hepatitis model. In α-GalCer-induced hepatitis models, TNF-α is critical in the development of liver injury. The mRNA expression and protein level of TNF-α in the liver from IDO-KO mice were more enhanced compared with those in WT mice. The phenotypes of intrahepatic lymphocytes from WT mice and IDO-KO mice treated with α-GalCer were analyzed by flow cytometry, and the numbers of CD49b(+) and CD11b(+) cells were found to have increased in IDO-KO mice. Moreover, as a result of the increase in the number of NK cells and macrophages in the liver of IDO-KO mice injected with α-GalCer, TNF-α secretion in these mice was greater than that in WT mice. Deficiency of IDO exacerbated liver injury in α-GalCer-induced hepatitis. IDO induced by proinflammatory cytokines may decrease the number of TNF-α-producing immune cells in the liver. Thus, IDO may suppress overactive immune response in the α-GalCer-induced hepatitis model.
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan. hito@gifu-u.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.forename: Masato
authors.initials: M
authors.lastname: Hoshi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohtaki
authors.forename: Ayako
authors.initials: A
authors.lastname: Taguchi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ando
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Osawa
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005699:Galactosylceramides; D006505:Hepatitis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000293:injuries / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D005699:Galactosylceramides; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C493154:alpha-galactosylceramide