TRAIL but not FasL and TNFα, regulates IL-33 expression in murine hepatocytes during acute hepatitis. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Hepatology Année : 2012

TRAIL but not FasL and TNFα, regulates IL-33 expression in murine hepatocytes during acute hepatitis.

Résumé

UNLABELLED: Interleukin (IL)-33, a member of the IL-1 cytokine family, positively correlates with acute hepatitis and chronic liver failure in mice and humans. IL-33 is expressed in hepatocytes and is regulated by natural killer T (NKT) cells during concanavalin A (ConA)-induced acute liver injury. Here, we investigated the molecular mechanisms underlying the expression of IL-33 during acute hepatitis. The expression of IL-33 and its regulation by death receptor pathways was investigated after the induction of ConA-acute hepatitis in wildtype (WT), perforin(-/-) , tumor necrosis factor related apoptosis inducing ligand (TRAIL)(-/-) , and NKT cell-deficient (CD1d(-/-) ) mice. In addition, we used a model of acute liver injury by administering Jo2/Fas-antibody or D-galactosamine-tumor necrosis factor alpha (TNFα) in WT mice. Finally, the effect of TRAIL on IL-33 expression was assessed in primary cultured murine hepatocytes. We show that IL-33 expression in hepatocytes is partially controlled by perforin during acute liver injury, but not by TNFα or Fas ligand (FasL). Interestingly, the expression of IL-33 in hepatocytes is blocked during ConA-acute hepatitis in TRAIL-deficient mice compared to WT mice. In contrast, administration of recombinant murine TRAIL associated with ConA-priming in CD1d-deficient mice or in vitro stimulation of murine hepatocytes by TRAIL but not by TNFα or Jo2 induced IL-33 expression in hepatocytes. The IL-33-deficient mice exhibited more severe ConA liver injury than WT controls, suggesting a protective effect of IL-33 in ConA-hepatitis. CONCLUSION: The expression of IL-33 during acute hepatitis is dependent on TRAIL, but not on FasL or TNFα.

Dates et versions

hal-00874194 , version 1 (17-10-2013)

Identifiants

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Muhammad Imran Arshad, Claire Piquet-Pellorce, Annie L'Helgoualc'H, Michel Rauch, Solène Patrat-Delon, et al.. TRAIL but not FasL and TNFα, regulates IL-33 expression in murine hepatocytes during acute hepatitis.. Hepatology, 2012, 56 (6), pp.2353-62. ⟨10.1002/hep.25893⟩. ⟨hal-00874194⟩
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