Interleukin-1 Receptor Antagonist Modulates Liver Inflammation and Fibrosis in Mice in a Model-Dependent Manner.
Details
Serval ID
serval:BIB_BA74E87252B5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interleukin-1 Receptor Antagonist Modulates Liver Inflammation and Fibrosis in Mice in a Model-Dependent Manner.
Journal
International journal of molecular sciences
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Publication state
Published
Issued date
14/03/2019
Peer-reviewed
Oui
Volume
20
Number
6
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
Interleukin-1 (IL-1)β and IL-1 receptor antagonist (IL-1Ra) have been proposed as important mediators during chronic liver diseases. We aimed to determine whether the modulation of IL-1β signaling with IL-1Ra impacts on liver fibrosis.
We assessed the effects of IL-1β on human hepatic stellate cells (HSC) and in mouse models of liver fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride treatment (CCl-4).
Human HSCs treated with IL-1β had increased IL-1β, IL-1Ra, and MMP-9 expressions in vitro. HSCs treated with IL-1β had reduced α-smooth muscle actin expression. These effects were all prevented by IL-1Ra treatment. In the BDL model, liver fibrosis and Kuppfer cell numbers were increased in IL-1Ra KO mice compared to wild type mice and wild type mice treated with IL-1Ra. In contrast, after CCl-4 treatment, fibrosis, HSC and Kupffer cell numbers were decreased in IL-1Ra KO mice compared to the other groups. IL-1Ra treatment provided a modest protective effect in the BDL model and was pro-fibrotic in the CCl-4 model.
We demonstrated bivalent effects of IL-1Ra during liver fibrosis in mice. IL-1Ra was detrimental in the CCl-4 model, whereas it was protective in the BDL model. Altogether these data suggest that blocking IL-1-mediated inflammation may be beneficial only in selective liver fibrotic disease.
We assessed the effects of IL-1β on human hepatic stellate cells (HSC) and in mouse models of liver fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride treatment (CCl-4).
Human HSCs treated with IL-1β had increased IL-1β, IL-1Ra, and MMP-9 expressions in vitro. HSCs treated with IL-1β had reduced α-smooth muscle actin expression. These effects were all prevented by IL-1Ra treatment. In the BDL model, liver fibrosis and Kuppfer cell numbers were increased in IL-1Ra KO mice compared to wild type mice and wild type mice treated with IL-1Ra. In contrast, after CCl-4 treatment, fibrosis, HSC and Kupffer cell numbers were decreased in IL-1Ra KO mice compared to the other groups. IL-1Ra treatment provided a modest protective effect in the BDL model and was pro-fibrotic in the CCl-4 model.
We demonstrated bivalent effects of IL-1Ra during liver fibrosis in mice. IL-1Ra was detrimental in the CCl-4 model, whereas it was protective in the BDL model. Altogether these data suggest that blocking IL-1-mediated inflammation may be beneficial only in selective liver fibrotic disease.
Keywords
Actins/genetics, Animals, Carbon Tetrachloride/adverse effects, Cell Count, Cells, Cultured, Disease Models, Animal, Gene Expression Regulation/drug effects, Gene Knockout Techniques, Humans, Interleukin 1 Receptor Antagonist Protein/genetics, Interleukin-1beta/genetics, Kupffer Cells/cytology, Kupffer Cells/drug effects, Kupffer Cells/immunology, Liver Cirrhosis/etiology, Liver Cirrhosis/genetics, Liver Cirrhosis/immunology, Male, Matrix Metalloproteinase 9/genetics, Mice, Up-Regulation, bile duct ligation, carbon tetracholoride, insulin, interleukin-1, interleukin-1 receptor antagonist, liver fibrosis
Pubmed
Web of science
Open Access
Yes
Create date
01/11/2023 14:09
Last modification date
13/04/2024 6:06
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