Journal Article

The Deficiency of Indoleamine 2,3-Dioxygenase Aggravates the CCl4-Induced Liver Fibrosis in Mice

Ishikawa, Tetsuya, Seishima, Mitsuru, Ito, Hiroyasu, Kanbe, Ayumu, Shimizu, Masahito, Saito, Kuniaki, Moriwaki, Hisataka, Hara, Akira, Ando, Kazuki, Arioka, Yuko, Ogiso, Hideyuki, Ando, Tatsuya

2016

Overview

In the present study, we examined the role of indoleamine 2,3-dioxygenase (IDO) in the development of CCl4-induced hepatic fibrosis. The liver fibrosis induced by repetitive administration with CCl4 was aggravated in IDO-KO mice compared to WT mice. In IDO-KO mice treated with CCl4, the number of several inflammatory cells and the expression of pro-inflammatory cytokines increased in the liver. In the results, activated hepatic stellate cells (HSCs) and fibrogenic factors on HSCs increased after repetitive CCl4 administration in IDO-KO mice compared to WT mice. Moreover, the treatment with l-tryptophan aggravated the CCl4-induced hepatic fibrosis in WT mice. Our findings demonstrated that the IDO deficiency enhanced the inflammation in the liver and aggravated liver fibrosis in repetitive CCl4-treated mice.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alanine Transaminase - genetics / Alanine Transaminase - immunology / Animals / Binding sites / Biology and Life Sciences / Carbon / Carbon Tetrachloride / CCL4 protein / Cell Survival - drug effects / Chemokine CCL2 - genetics / Chemokine CCL2 - immunology / Clinical medicine / Cytokines / Dendritic cells / Experiments / Fibrosis / Gene expression / Health sciences / Hepatic Stellate Cells - drug effects / Hepatic Stellate Cells - immunology / Hepatic Stellate Cells - pathology / Hepatitis / Hepatocytes - drug effects / Hepatocytes - immunology / Hepatocytes - pathology / Immunophenotyping / Indoleamine-Pyrrole 2,3,-Dioxygenase - deficiency / Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics / Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology / Inflammation / Interleukin-1beta - genetics / Interleukin-1beta - immunology / Interleukin-6 - genetics / Interleukin-6 - immunology / Internal medicine / Laboratory animals / Leukocytes, Mononuclear - drug effects / Leukocytes, Mononuclear - immunology / Leukocytes, Mononuclear - pathology / Liver / Liver - drug effects / Liver - immunology / Liver - pathology / Liver cirrhosis / Liver Cirrhosis - chemically induced / Liver Cirrhosis - genetics / Liver Cirrhosis - immunology / Liver Cirrhosis - pathology / Male / Medicine / Medicine and Health Sciences / Metabolites / Mice / Mice, Inbred C57BL / Mice, Knockout / Olive oil / Physical Sciences / Proto-Oncogene Proteins c-sis - genetics / Proto-Oncogene Proteins c-sis - immunology / Rodents / Stellate cells / Tryptophan / Tryptophan - pharmacology / Tryptophan 2,3-dioxygenase / Tumor Necrosis Factor-alpha - genetics / Tumor Necrosis Factor-alpha - immunology / Tumor necrosis factor-TNF / University graduates