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Aging and disease    2019, Vol. 10 Issue (5) : 1094-1108     DOI: 10.14336/AD.2019.0116
Review Article |
Pyroptosis in Liver Disease: New Insights into Disease Mechanisms
Jiali Wu1, Su Lin1,*, Bo Wan2, Bharat Velani3, Yueyong Zhu1
1Liver research center of the First Affiliated Hospital of Fujian Medical University, Fujian 350005, China
2Faculty of Life Sciences and Medicine, King’s College London, London SE1 1UL, United Kingdom
3Basildon and Thurrock University Hospitals NHS Foundation Trust, Nethermayne, Basildon, Essex SS16 5NL, United Kingdom
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There has been increasing interest in pyroptosis as a novel form of pro-inflammatory programmed cell death. The mechanism of pyroptosis is significantly different from other forms of cell death in its morphological and biochemical features. Pyroptosis is characterized by the activation of two different types of caspase enzymes—caspase-1 and caspase-4/5/11, and by the occurrence of a proinflammatory cytokine cascade and an immune response. Pyroptosis participates in the immune defense mechanisms against intracellular bacterial infections. On the other hand, excessive inflammasome activation can induce sterile inflammation and eventually cause some diseases, such as acute or chronic hepatitis and liver fibrosis. The mechanism and biological significance of this novel form of cell death in different liver diseases will be evaluated in this review. Specifically, we will focus on the role of pyroptosis in alcoholic and non-alcoholic fatty liver disease, as well as in liver failure. Finally, the therapeutic implications of pyroptosis in liver diseases will be discussed.

Keywords pyroptosis      NLRP3      fatty liver disease      liver failure     
Corresponding Authors: Lin Su   
About author:

Present address: Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore.

Issue Date: 27 September 2019
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Wu Jiali
Lin Su
Wan Bo
Velani Bharat
Zhu Yueyong
Cite this article:   
Wu Jiali,Lin Su,Wan Bo, et al. Pyroptosis in Liver Disease: New Insights into Disease Mechanisms[J]. Aging and disease, 2019, 10(5): 1094-1108.
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Cell deathActivated byEffectorMorphologyResult cell corpseinflammationrefs
PyroptosisPAMPs and DAMPscaspase-1 or
lyticpore-induced intracellular trapyes[4]
necrosisphysical and chemical stimulation-lyticpore-induced intracellular trapyes[8]
apoptosisintrinsic or
extrinsic pathways
caspase-3/6/7non-lyticapoptotic bodyno[9]
Table 1  Comparison of different forms of cell death
Figure 1.  Pathways of pyroptosis. There are two different pyroptotic pathways. The canonical pyroptosis is dependent on the activation of caspase-1 by inflammasomes, which can recognize PAMPs and DAMPs. Compared to canonical pyroptosis, noncanonical pyroptosis is mediated by the activation of caspase-1 and caspase-4/5 (caspase-11 in mice), which can be directly activated by LPS independent of TLR4. Upon activation, these caspases cleave gasdermin D then bind to lipids in the plasma membrane and form oligomeric pores leading to the release of cellular contents and cell death. Caspase-4/5/11 activates the Pannexin-1 channel and then opens the P2X7 pore to mediate pyroptosis. Meanwhile, activation of caspase-1 results in the cleavage of pro-IL-1β and pro-IL-18 and the production of mature cytokines. PAMPS, pathogen-associated molecular patterns; DAMPS, damage-associated molecular patterns; IL-1β, Interleukin-1β; IL-18, Interleukin-18.
Therapeutic targetsMoleculesDiseasesSubjectsReferences
NLPR3GlyburideAcute liver injury
(CLP model)
male C57BL/6 mice[26]
(NLRP3 inhibitor)
(D-Gal challenge)
male C57BL/6 mice[129]
EPOSepsis related liver injury
(LPS challenge)
TUDCANASHobese mice[77]
Male C57BL/6 mice[156]
SilybinNAFLDMale C57BL/6 mice[153]
DihydroquercetinALDMale C57BL/6 mice[146]
Chlorogenic acidAcute liver injury
male Sprague-Dawley rats[154]
ScutellarinSepsis related liver injury
(intraperitoneally injection of Escherichia coli)
Female C57BL/6 mice[144]
(caspase-1 inhibitor)
Acute liver injury
(MSN administration)
male C57BL/6 mice[61]
IDN 6556
(pan-caspase inhibitor)
IDN 6556
(pan-caspase inhibitor)
HCVHCV patients[158]
(pan-caspase inhibitor)
HCVHCV patients[159]
Cathepsin B inhibitorSIRS /sepsis
(LPS challenge)
Human KCs[68]
(IL-1 inhibitor)
(D-GalN/LPS administration)
Table 2  Potential anti-pyroptotic targets in liver disease.
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