Advertisement

The inflammasome in liver disease

  • Alexander Wree
    Correspondence
    Corresponding authors. Addresses: Medizinische Klinik III, Uniklinik RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany. Tel.: +49 (0)241 80 37732 (A. Wree), or Dipartimento di Medicina Sperimentale e Clinica, Largo Brambilla, 3, I50134 Florence, Italy. Tel.: +39 055 7945425 (F. Marra).
    Affiliations
    Department of Internal Medicine III, University Hospital, RWTH Aachen, Germany

    Department of Pediatric Gastroenterology, University of California San Diego (UCSD), and Rady Children’s Hospital, San Diego, CA, United States
    Search for articles by this author
  • Fabio Marra
    Correspondence
    Corresponding authors. Addresses: Medizinische Klinik III, Uniklinik RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany. Tel.: +49 (0)241 80 37732 (A. Wree), or Dipartimento di Medicina Sperimentale e Clinica, Largo Brambilla, 3, I50134 Florence, Italy. Tel.: +39 055 7945425 (F. Marra).
    Affiliations
    Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Italy

    Research Center DENOTHE, University of Florence, Italy
    Search for articles by this author
Published:September 19, 2016DOI:https://doi.org/10.1016/j.jhep.2016.07.002
      Inflammation is a common feature of most chronic liver diseases. Molecules derived from microbial or viral pathogens, commonly known as pathogen-associated molecular patterns (PAMPs), or sterile stimuli released from damaged hepatic cells, known as damage-associated molecular patterns (DAMPs) can trigger the activation of inflammation [
      • Strowig T.
      • Henao-Mejia J.
      • Elinav E.
      • et al.
      Inflammasomes in health and disease.
      ]. Inflammasomes are multi-protein complexes expressed in different hepatic cells, and are characterized by a nucleotide-binding oligomerization domain (NOD)-like receptors (NLR), the sensor component of the inflammasome system. NLRs form complexes with effector molecules, e.g., pro-caspase-1, and adapter molecules, e.g., apoptosis-associated speck like CARD-domain containing protein (ASC).

      Abbreviations:

      A20 (Tumor necrosis factor, alpha-induced protein 3), ALD (alcoholic liver disease), AhR (aryl hydrocarbon receptor), ASC (CARD-domain containing protein), ATP (adenosine triphosphate), CARD8 (caspase recruitment domain), Casp1 (caspase-1), CCL2 (CC-chemokine ligand 2), DAMPs (danger associated molecular pattern), DILI (drug induced liver injury), ER (endoplasmic reticulum), FFA (free fatty acids), GPSM3 (G protein signaling modulator-3), HCC (hepatocellular carcinoma), HCV (hepatitis C virus), HMGB1 (high-mobility group protein 1), IL (interleukin), NASH (non-alcoholic steatohepatitis), NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells), NLR (NOD-like receptors), NO (nitric oxide), NOD (nucleotide-binding oligomerization domain), PAMPs (pathogen-associated molecular pattern), PX27 (P2X purinoceptor 7), ROS (reactive oxygen species), TLR (toll-like receptors), TNF-α (tumor necrosis factor alpha)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Strowig T.
        • Henao-Mejia J.
        • Elinav E.
        • et al.
        Inflammasomes in health and disease.
        Nature. 2012; 481: 278-286
        • Kubes P.
        • Mehal W.Z.
        Sterile inflammation in the liver.
        Gastroenterology. 2012; 143: 1158-1172
        • Jo E.-K.
        • Kim J.K.
        • Shin D.-M.
        • et al.
        Molecular mechanisms regulating NLRP3 inflammasome activation.
        Cell Mol Immunol. 2016; 13: 148-159
        • Tilg H.
        • Moschen A.R.
        • Szabo G.
        Interleukin-1 and inflammasomes in ALD/AAH and NAFLD/NASH.
        Hepatology. 2016; 64: 955-965
        • Petrasek J.
        • Bala S.
        • Csak T.
        • et al.
        IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice.
        J Clin Invest. 2012; 122: 3476-3489
        • Wree A.
        • Eguchi A.
        • McGeough M.D.
        • et al.
        NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice.
        Hepatology. 2014; 59: 898-910
        • Voican C.S.
        • Njike-Nakseu M.
        • Boujedidi H.
        • et al.
        Alcohol withdrawal alleviates adipose tissue inflammation in patients with alcoholic liver disease.
        Liver Int. 2015; 35: 967-978
        • Csak T.
        • Ganz M.
        • Pespisa J.
        • et al.
        Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells.
        Hepatology. 2011; 54: 133-144
        • Gieling R.G.
        • Wallace K.
        • Han Y.P.
        Interleukin-1 participates in the progression from liver injury to fibrosis.
        Am J Physiol Gastrointest Liver Physiol. 2009; 296: G1324-G1331
        • McRae S.
        • Iqbal J.
        • Sarkar-Dutta M.
        • et al.
        Hepatitis C virus-induced NLRP3-Inflammasome Activates the Sterol Regulatory Element Binding Protein (SREBP) and Regulates Lipid Metabolism.
        J Biol Chem. 2016; 291: 3254-3267
        • Han Y.
        • Chen Z.
        • Hou R.
        • et al.
        Expression of AIM2 is correlated with increased inflammation in chronic hepatitis B patients.
        Virol J. 2015; 12: 129
        • Imaeda A.B.
        • Watanabe A.
        • Sohail M.A.
        • et al.
        Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome.
        J Clin Invest. 2009; 119: 305-314
        • Williams C.D.
        • Farhood A.
        • Jaeschke H.
        Role of caspase-1 and interleukin-1beta in acetaminophen-induced hepatic inflammation and liver injury.
        Toxicol Appl Pharmacol. 2010; 247: 169-178
        • Wei Q.
        • Mu K.
        • Li T.
        • et al.
        Deregulation of the NLRP3 inflammasome in hepatic parenchymal cells during liver cancer progression.
        Lab Invest. 2014; 94: 52-62
        • Fan S.H.
        • Wang Y.Y.
        • Lu J.
        • et al.
        Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma cells by inhibition of NLRP3 inflammasome.
        PLoS One. 2014; 9 (e89961)