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Mice deficient in hepatocyte-specific IL-1Ra show delayed resolution of concanavalin A-induced hepatitis

Published in European Journal of Immunology. 2012, vol. 42, no. 5, p. 1294-303
Abstract Interleukin-1 receptor antagonist (IL-1Ra) is a specific IL-1 inhibitor that possesses anti-inflammatory activities. Several studies in human and mouse suggested a protective role for IL-1Ra in liver inflammation, and we previously demonstrated that hepatocytes produce high levels of IL-1Ra in response to inflammatory challenge in vitro and in vivo. In the present study, we investigated the production and the biological function of hepatocyte-derived IL-1Ra in concanavalin A (ConA)-induced hepatitis in mice. We show that the injured liver produces large amounts of IL-1Ra and that secreted and intracellular IL-1Ra isoforms are produced with different kinetics during the course of hepatitis. By using hepatocyte-specific IL-1Ra-deficient mice (IL-1Ra(ΔH)), we demonstrate that hepatocytes represent the major cellular source of local IL-1Ra. Most interestingly, hepatic necrosis and inflammation were increased in IL-1Ra(ΔH) as compared with wild-type mice during the late phase of the disease, leading to a delayed resolution of hepatitis in IL-1Ra(ΔH) mice. In conclusion, our results show that the local production of IL-1Ra by hepatocytes contributes to the resolution of hepatitis.
Keywords AnimalsConcanavalin A/toxicityCytokines/analysisHepatitis/genetics/immunology/pathologyHepatocytes/drug effects/immunologyInterleukin 1 Receptor Antagonist Protein/genetics/immunologyLiver/immunology/secretionMaleMiceMice, Inbred C57BLNecrosis/immunology
PMID: 22539301
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Article (Published version) (1.2 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research groups Métastases du foie (657)
Etudes et traitement de l'hépatite C et B (554)
Mécanisme de l'inflammation articulaire (44)
(ISO format)
LAMACCHIA, Céline et al. Mice deficient in hepatocyte-specific IL-1Ra show delayed resolution of concanavalin A-induced hepatitis. In: European Journal of Immunology, 2012, vol. 42, n° 5, p. 1294-303. https://archive-ouverte.unige.ch/unige:27570

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Deposited on : 2013-04-25

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