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

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

doi:10.1371/journal.pone.0162183

Cited by 20 publications

(21 citation statements)

References 38 publications

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“…Increased infiltration of immune cells and increased expression of proinflammatory cytokines was noticed in fibrotic livers of CCl 4 ‐treated IDO‐deficient mice. Aggravated liver fibrosis was also seen in mice that received IDO inhibitor, 1‐methyl‐ dl ‐tryptophan . In line with these findings, several clinical trials reported beneficent effects of MSCs in the therapy of cirrhosis .…”

Section: Introductionsupporting

confidence: 60%

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Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

et al. 2017

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Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed. Under inflammatory conditions, MSCs-derived factors suppress both innate and adaptive immunity by attenuating maturation and capacity for antigen presentation of dendritic cells, by inducing polarization of macrophages towards alternative phenotype, by inhibiting activation and proliferation of T and B lymphocytes and by reducing cytotoxicity of NK and NKT cells. In this review, we emphasized current findings regarding immuno-modulatory effects of MSC-derived factors and emphasize their potential in the therapy of immune-mediated diseases. © 2017 BioFactors, 43(5):633-644, 2017.

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Section: Introductionsupporting

confidence: 60%

“…Protective and immuno‐modulatory role of IDO has been recently described in animal model of liver fibrosis induced by carbon tetra chloride (CCl 4 ) . Increased infiltration of immune cells and increased expression of proinflammatory cytokines was noticed in fibrotic livers of CCl 4 ‐treated IDO‐deficient mice.…”

Section: Introductionmentioning

confidence: 98%

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

et al. 2017

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“…Protective and immunomodulatory role of IDO has been recently described in CCl 4 ‐induced liver fibrosis . Increased infiltration of immune cells and increased expression of pro‐inflammatory cytokines was noticed in fibrotic livers of CCl 4 ‐treated IDO‐deficient mice.…”

Section: Discussionmentioning

confidence: 88%

“…Increased infiltration of immune cells and increased expression of pro‐inflammatory cytokines was noticed in fibrotic livers of CCl 4 ‐treated IDO‐deficient mice. Aggravated liver fibrosis was also seen in mice that received IDO inhibitor .…”

Section: Discussionmentioning

confidence: 92%

Mesenchymal stem cells attenuate liver fibrosis by suppressing Th17 cells - an experimental study

et al. 2017

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This study investigates molecular and cellular mechanisms involved in mesenchymal stem cell (MSC)-mediated modulation of IL-17 signaling during liver fibrosis. Mice received CCl (1 μl/g intraperitoneally) twice/week for 1 month. MSCs (1 × 10 ), or MSC-conditioned medium (MSC-CM), were intravenously injected 24 h after CCl and on every 7th day. Liver fibrosis was determined by macroscopic examination, histological analysis, Sirius red staining, and RT-PCR. Serum levels of cytokines, indoleamine 2,3-dioxygenase (IDO), and kynurenine were determined by ELISA. Flow cytometry was performed to identify liver-infiltrated cells. In vitro, CD4 T cells were stimulated and cultured with MSCs. 1-methyltryptophan was used for inhibition of IDO. MSCs significantly attenuated CCl -induced liver fibrosis by decreasing serum levels of inflammatory IL-17, increasing immunosuppressive IL-10, IDO, and kynurenine, reducing number of IL-17 producing Th17 cells, and increasing percentage of CD4 IL-10 T cells. Injection of MSC-CM resulted with attenuated fibrosis accompanied with the reduced number of Th17 cells in the liver and decreased serum levels of IL-17. MSC-CM promoted expansion of CD4 FoxP3 IL-10 T regulatory cells and suppressed proliferation of Th17 cells. This phenomenon was completely abrogated in the presence of IDO inhibitor. MSCs, in IDO-dependent manner, suppress liver Th17 cells which lead to the attenuation of liver fibrosis.

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“…It is well documented that CCl 4 intoxication can induce liver lesion, cirrhosis and hepatocarcinoma [21,22], thus being a well-established model of liver damage. In the present study, CCl 4 administration increased the serum levels of ALT, AST, ALP.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effects of Standardized Extracts from an Ancient Italian Apple Variety (Mela Rosa dei Monti Sibillini) against Carbon Tetrachloride (CCl4)-Induced Hepatotoxicity in Rats

et al. 2020

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The aim of this research was to examine the effect of the hydroalcoholic extracts from the peel (APE) and pulp (APP) of a traditional apple cultivar from central Italy (Mela Rosa dei Monti Sibillini) on CCl4-induced hepatotoxicity in rats. Phytoconstituents were determined by liquid chromatography–mass spectrometry (LC-MS) analysis showing an abundance of proanthocyanidins and flavonol derivatives together with the presence of annurcoic acid in APE. Wistar rats received APE/APP (30 mg/kg oral administration) for three days before CCl4 injection (2 mL/kg intraperitoneal once on the third day). Treatment with both APE and APP prior to CCl4 injection significantly decreased the serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) compared to the CCl4 group. Besides, pretreatment with APE reversed the CCl4 effects on superoxide dismutase (SOD), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) and interleukin-1beta (IL-1β) levels in liver tissue in rats and reduced tissue damage as shown in hematoxylin and eosin staining. These results showed that this ancient Italian apple is worthy of use in nutraceuticals and dietary supplements to prevent and/or protect against liver disorders.

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

Cited by 20 publications

References 38 publications

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

Mesenchymal stem cells attenuate liver fibrosis by suppressing Th17 cells - an experimental study

Hepatoprotective Effects of Standardized Extracts from an Ancient Italian Apple Variety (Mela Rosa dei Monti Sibillini) against Carbon Tetrachloride (CCl4)-Induced Hepatotoxicity in Rats

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