| First Author | Ito H | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 8 | Pages | 4554-60 |
| PubMed ID | 20844202 | Mgi Jnum | J:164734 |
| Mgi Id | MGI:4835098 | Doi | 10.4049/jimmunol.0904173 |
| Citation | Ito H, et al. (2010) Ability of IDO to attenuate liver injury in alpha-galactosylceramide-induced hepatitis model. J Immunol 185(8):4554-60 |
| abstractText | 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 alpha-galactosylceramide (alpha-GalCer)-induced hepatitis. The increase in IDO expression in the liver of wild-type (WT) mice administered alpha-GalCer was confirmed by real-time PCR, Western blotting, and IDO immunohistochemical analysis. The serum alanine aminotransferase levels in IDO-knockout (KO) mice after alpha-GalCer injection significantly increased compared with those in WT mice. 1-Methyl-D-tryptophan also exacerbated liver injury in this murine hepatitis model. In alpha-GalCer-induced hepatitis models, TNF-alpha is critical in the development of liver injury. The mRNA expression and protein level of TNF-alpha 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 alpha-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 alpha-GalCer, TNF-alpha secretion in these mice was greater than that in WT mice. Deficiency of IDO exacerbated liver injury in alpha-GalCer-induced hepatitis. IDO induced by proinflammatory cytokines may decrease the number of TNF-alpha-producing immune cells in the liver. Thus, IDO may suppress overactive immune response in the alpha-GalCer-induced hepatitis model. |
