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Interleukin-1 receptor antagonist modulates liver inflammation and fibrosis in mice in a model-dependent manner

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Published in International Journal of Molecular Sciences. 2019, vol. 20, no. 6, 1295
Abstract Background: 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. Methods: 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). Results: 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. Conclusions: 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 Liver fibrosisInterleukin-1 receptor antagonistInterleukin-1Bile duct ligationCarbon tetracholorideInsulin
PMID: 30875826
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Research groups Etudes et traitement de l'hépatite C et B (554)
Transplantation et hépatologie (905)
Swiss National Science Foundation: PP00P3_165837
(ISO format)
MEIER, Raphaël et al. Interleukin-1 receptor antagonist modulates liver inflammation and fibrosis in mice in a model-dependent manner. In: International Journal of Molecular Sciences, 2019, vol. 20, n° 6, p. 1295. doi: 10.3390/ijms20061295 https://archive-ouverte.unige.ch/unige:115226

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Deposited on : 2019-03-22

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