Ability of IDO to attenuate liver injury in α-galactosylceramide- induced hepatitis model

Hiroyasu Ito, Masato Hoshi, Hirofumi Ohtaki, Ayako Taguchi, Kazuki Ando, Tetsuya Ishikawa, Yosuke Osawa, Akira Hara, Hisataka Moriwaki, Kuniaki Saito, Mitsuru Seishima

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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.

Original languageEnglish
Pages (from-to)4554-4560
Number of pages7
JournalJournal of Immunology
Volume185
Issue number8
DOIs
Publication statusPublished - 15-10-2010
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Ito, H., Hoshi, M., Ohtaki, H., Taguchi, A., Ando, K., Ishikawa, T., Osawa, Y., Hara, A., Moriwaki, H., Saito, K., & Seishima, M. (2010). Ability of IDO to attenuate liver injury in α-galactosylceramide- induced hepatitis model. Journal of Immunology, 185(8), 4554-4560. https://doi.org/10.4049/jimmunol.0904173