The Deficiency of Indoleamine 2,3-Dioxygenase Aggravates the CCl4-Induced Liver Fibrosis in Mice.
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.
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Hideyuki
H
Ogiso
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Hiroyasu
H
Ito
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Tatsuya
T
Ando
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Yuko
Y
Arioka
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Ayumu
A
Kanbe
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Kazuki
K
Ando
Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan.
Tetsuya
T
Ishikawa
Human Health Sciences, Kyoto University Graduate School of Medicine and Faculty of Medicine, Kyoto, Japan.
Kuniaki
K
Saito
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
Akira
A
Hara
First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Hisataka
H
Moriwaki
First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Masahito
M
Shimizu
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Mitsuru
M
Seishima
D000410:Alanine Transaminase / Q000235:genetics / Q000276:immunology; D000818:Animals; D002251:Carbon Tetrachloride; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D016130:Immunophenotyping; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000276:immunology; D014364:Tryptophan / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C587672:IL1B protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053583:Interleukin-1beta; D015850:Interleukin-6; D020574:Proto-Oncogene Proteins c-sis; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D014364:Tryptophan; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase