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TRAIL but not FasL and TNFα, regulates IL‐33 expression in murine hepatocytes during acute hepatitis
Author(s) -
Arshad Muhammad Imran,
PiquetPellorce Claire,
L'Helgoualc'h Annie,
Rauch Michel,
PatratDelon Solène,
Ezan Frédéric,
LucasClerc Catherine,
Nabti Sabrina,
Lehuen Agnès,
Cubero Francisco Javier,
Girard JeanPhilippe,
Trautwein Christian,
Samson Michel
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25893
Subject(s) - perforin , fas ligand , tumor necrosis factor alpha , liver injury , concanavalin a , immunology , hepatitis , cytokine , interleukin , biology , medicine , apoptosis , immune system , programmed cell death , endocrinology , in vitro , cd8 , biochemistry
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. (H EPATOLOGY 2012)