Role of pyroptosis in liver diseases

https://doi.org/10.1016/j.intimp.2020.106489Get rights and content

Highlights

  • Pyroptosis is known as programmed cell death.

  • There are two types of signaling pathways, such as caspase-1, and caspase-4/5/11 mediated pathways, involved in pyroptosis.

  • Pyroptosis plays crucial roles in the pathogenesis and progression of various liver diseases.

  • NLRP3 inflammasome inhibitors can markedly inhibit pyroptosis, which can prevent the liver diseases.

  • So, Targeting pyroptosis can be a new potential therapeutic target for the treatment of liver diseases in the near future.

Abstract

Pyroptosis is known as a novel form of pro-inflammatory cell death program, which is exceptional from other types of cell death programs. Particularly, pyroptosis is characterized by Gasdermin family-mediated pore formation and subsequently cellular lysis, also release of several pro-inflammatory intracellular cytokines. In terms of mechanism, there are two signaling pathways involved in pyroptosis, including caspase-1, and caspase-4/5/11 mediated pathways. However, pyroptosis plays important roles in immune defense mechanisms. Recent studies have demonstrated that pyroptosis plays significant roles in the development of liver diseases. In our review, we have focused on the role of pyroptosis based on the molecular and pathophysiological mechanisms in the development of liver diseases. We have also highlighted targeting of pyroptosis for the therapeutic implications in liver diseases in the near future.

Introduction

In the process of individual growth and development, cell death can occur at any time. It is a universal life phenomenon in biology, which plays an important role in the growth, development, and homeostasis of multicellular organisms [1]. It is believed that there are two ways of cell death: cell necrosis, and programmed cell death. The latter includes programmed cell death, and apoptosis [2]. In recent years, researchers have found new ways of programmed cell death, including cell swelling, autophagy, and pyroptosis. Unlike apoptosis and necrosis, pyroptosis is dependent on inflammatory caspase-1, and caspase-4/5/11 with inflammation. Caspase is activated by various microbial infections, and several endogenous risk signals. However, pyroptosis plays critical roles in several diseases, including infectious diseases, cardiovascular diseases, central nervous system diseases, and tumors [3], [4], [5], [6]. Therefore, this paper reviews the molecular mechanism of pyroptosis and its role in the pathogenesis and progression of various liver diseases.

Section snippets

History of pyroptosis

The morphological characteristic and function of pyroptosis were first observed in macrophages infected with Gram-negative bacteria called Shigella flexneri in 1992, which was mistaken for the morphological change of apoptosis [7]. Similar phenotypes were firstly observed in macrophages infected with Salmonella in 1999 [8]. Further studies have shown that both selective caspase-1 inhibitors and caspase-1 gene knockout can effectively block the cell death induced by Shigella flexneri, while

Canonical pyroptotic pathways

In terms of mechanism, pyroptotic processes are well preserved in different cell types which have been proved to involve the activation of typical caspase-1 and atypical caspase-4/5/11 (human caspase-4/5, and mouse caspase-11) [20]. Pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) are detected in the typical pyroptotic signaling pathways by the nucleotide-binding oligomerization domain (NOD) like receptor (NLRP3, NLRP1, NLRC4, NLRP9 and NLRP6),

Role of pyroptosis in liver diseases

Generally, moderate pyroptosis regulates to remove infected cells in time. With the increasing incidence of liver diseases, it has recently become a serious health issue. Some liver diseases gradually develop into cirrhosis, as well as liver cancer, which in turn can become a massive threat to human life worldwide [61]. In addition, recent studies have reported that pyroptosis can play significant roles in the progression of liver diseases [62]. During imbalanced intestinal floral condition,

Targeting pyroptosis for the therapeutic implications of liver diseases

Targeting pyroptosis is a promising treatment option for liver diseases, which has been receiving attention to researchers or clinicians worldwide. At present, there are two main strategies to suppress pyroptosis. One is to inhibit NLRP3 inflammasome through the regulatory pathways; for example-MCC950 is called as an NLRP3 inhibitor, which can effectively reduce cholestetic liver injury, and inflammation in bile duct ligation (BDL) mice model [100]. So, this study demonstrated that MCC950

Summary

So far, two types of pyroptosis signaling pathways have been described as typical caspase-1 dependent, and non-abnormal caspase-4/5/11 mediated signaling pathways. New evidence suggests that the NLRP3 inflammasome activation is an important regulator of pyroptosis process, which plays various roles in the development of liver diseases, including NAFLD, ALD, ACLF, HBV and HCV, AIH, HCC, and fibrosis (Fig. 5). However, despite these new developments, little study has been done on pyroptosis until

Declaration of Competing Interest

The authors declare that there is no conflict of interest.

Acknowledgment

We are giving thanks to Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China to conduct this study and for the valuable supports.

References (169)

  • D. Yang et al.

    Caspase-11 requires the pannexin-1 channel and the purinergic P2X7 pore to mediate pyroptosis and endotoxic shock

    Immunity

    (2015)
  • Q.R. Lin et al.

    Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway

    Toxicol. Appl. Pharmacol.

    (2016)
  • S. Feng et al.

    Mechanisms of gasdermin family members in inflammasome signaling and cell death

    J. Mol. Biol.

    (2018)
  • J.H. Chen et al.

    IgG4-related disease and the liver

    Gastroenterol. Clin. North Am.

    (2017)
  • V.I. Maltez et al.

    Inflammasomes coordinate pyroptosis and natural killer cell cytotoxicity to clear infection by a ubiquitous environmental bacterium

    Immunity

    (2015)
  • L. Xu et al.

    Cell biology of infection by Legionella pneumophila

    Microbes Infect.

    (2013)
  • H. Zhao et al.

    VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia-reperfusion injury in rats

    Am. J. Transpl.: Off. J. Am. Soc. Transpl. Am. Soc. Transplant Surg.

    (2018)
  • H. Guo et al.

    The relevance of pyroptosis in the pathogenesis of liver diseases

    Life Sci.

    (2019)
  • A. Eguchi et al.

    Biomarkers of liver cell death

    J. Hepatol.

    (2014)
  • J.I. Beier et al.

    Pyroptosis: An inflammatory link between NAFLD and NASH with potential therapeutic implications

    J. Hepatol.

    (2018)
  • B. Xu et al.

    Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice

    J. Hepatol.

    (2018)
  • J. Qu et al.

    The selective NLRP3 inflammasome inhibitor MCC950 alleviates cholestatic liver injury and fibrosis in mice

    Int. Immunopharmacol.

    (2019)
  • G. Kroemer et al.

    Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009

    Cell Death Differ.

    (2009)
  • S. Elmore

    Apoptosis: a review of programmed cell death

    Toxicol. Pathol.

    (2007)
  • T. Dong et al.

    Using small molecules to dissect non-apoptotic programmed cell death: necroptosis, ferroptosis, and pyroptosis

    Chembiochem: a Eur. J. Chem. Biol.

    (2015)
  • X. Xia et al.

    The role of pyroptosis in cancer: pro-cancer or pro-“host”?

    Cell Death Dis.

    (2019)
  • S.M. Man, R. Karki, T.D. Kanneganti, Molecular mechanisms and functions of pyroptosis, inflammatory caspases and...
  • X. Xia, X. Wang, Z. Cheng, W. Qin, L. Lei, J. Jiang, J. Hu, The role of pyroptosis in cancer: pro-cancer or...
  • S.L. Fink et al.

    Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells

    Infect. Immun.

    (2005)
  • S. Achouri et al.

    The frequency and duration of Salmonella-macrophage adhesion events determines infection efficiency

    Philos. Trans. R. Soc. Lond. B Biol. Sci.

    (2015)
  • X. Xia et al.

    The role of pyroptosis in cancer: pro-cancer or pro-“host”?

    Cell Death Dis.

    (2019)
  • E.A. Miao et al.

    Caspase-1-induced pyroptotic cell death

    Immunol. Rev.

    (2011)
  • L. Sun et al.

    Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome

    Cell Death Dis.

    (2019)
  • J.D. Edgeworth et al.

    Cytotoxicity and interleukin-1beta processing following Shigella flexneri infection of human monocyte-derived dendritic cells

    Eur. J. Immunol.

    (2002)
  • A. Wree et al.

    NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice

    Hepatology

    (2014)
  • L. DiPeso, D.X. Ji, R.E. Vance, Cell death and cell lysis are separable events during pyroptosis, 3 (2017)...
  • H. Russo, J. Rathkey, A. Boyd-Tressler, M. Katsnelson, D. Abbott, G....
  • F. Wang, R. Gomez-Sintes, P. Boya, Lysosomal membrane permeabilization and cell death, 19(12) (2018)...
  • A.P. Demchenko

    Beyond annexin V: fluorescence response of cellular membranes to apoptosis

    Cytotechnology

    (2013)
  • Y. Jin et al.

    Sevoflurane combined with ATP activates caspase-1 and triggers caspase-1-dependent pyroptosis in murine J774 macrophages

    Inflammation

    (2013)
  • T. Liu et al.

    NOD-like receptor family, pyrin domain containing 3 (NLRP3) contributes to inflammation, pyroptosis, and mucin production in human airway epithelium on rhinovirus infection

    J. Allergy Clin. Immunol.

    (2019)
  • M.D. Sanchez-Nino et al.

    Uromodulin, inflammasomes, and pyroptosis

    J. Am. Soc. Nephrol.: JASN

    (2012)
  • L.D. Cunha et al.

    Subversion of inflammasome activation and pyroptosis by pathogenic bacteria

    Front. Cell. Infect. Microbiol.

    (2013)
  • Q. Lei et al.

    NF-kappaB-gasdermin D (GSDMD) axis couples oxidative stress and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome-mediated cardiomyocyte pyroptosis following myocardial infarction

    Med. Sci. Monit.: Int. Med. J. Exp. Clin. Res.

    (2018)
  • W. Liu et al.

    NLRP6 induces pyroptosis by activation of caspase-1 in gingival fibroblasts

    J. Dent. Res.

    (2018)
  • T. Qiu et al.

    Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway

    Cell Death Dis.

    (2018)
  • A. Balakrishnan et al.

    Guanylate binding proteins facilitate caspase-11-dependent pyroptosis in response to type 3 secretion system-negative Pseudomonas aeruginosa

    Cell Death Discovery

    (2018)
  • C.L. Case et al.

    Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila

    Proc. Natl. Acad. Sci. USA

    (2013)
  • X.Q. Li et al.

    Knockdown of the AIM2 molecule attenuates ischemia-reperfusion-induced spinal neuronal pyroptosis by inhibiting AIM2 inflammasome activation and subsequent release of cleaved caspase-1 and IL-1beta

    Neuropharmacology

    (2019)
  • O. Schnappauf et al.

    The pyrin inflammasome in health and disease

    Front. Immunol.

    (2019)
  • Cited by (56)

    View all citing articles on Scopus
    View full text