Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance |
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Authors: | Hilal Ahmad Khan Muhammad Zishan Ahmad Junaid Ali Khan Muhammad Imran Arshad |
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Affiliation: | 1. Institute of Microbiology University of Agriculture,Faisalabad,Pakistan;2. Institute of Pharmacy,Physiology and Pharmacology University of Agriculture,Faisalabad,Pakistan;3. Department of Pathology,The University of Faisalabad (TUF) Faisalabad,Pakistan |
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Abstract: | BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepato-toxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions.DATA SOURCES: The data of mouse hepatic models and rele-vant human liver diseases presented in this review are system-atically collected from PubMed, ScienceDirect and the Web of Science databases published in English.RESULTS: The hepatotoxic liver injury in mice induced by the metabolites of CCl4, acetaminophen or alcohol represent ne-crotic cell death with activation of cytochrome pathway, for-mation of reactive oxygen species (ROS) and mitochondrial damage. The Fas or TNF-α induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrat-ed the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The α-GalCer-induced liver injury was mediated by TNF-α. The LPS-induced hepa-titis involved TNF-α, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly(I:C) induced liver injury was mediated by natural killer cells and TNF-α signaling. The necrotic ischemia-reperfusion liver injury was mediated byhypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune cells and cell death mediators in viral hepatitis (HBV, HCV), drug-induced liver injury, non-alcohol-ic fatty liver disease and alcoholic liver disease in human were discussed.CONCLUSIONS: The mouse animal models of hepatitis pro-vide a parallel approach for the study of human liver pathol-ogy. Blocking or stimulating the pathways associated with liver cell death could unveil the novel therapeutic strategies in the management of liver diseases. |
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Keywords: | liver immunobiology hepatitis therapy mode of cell death |
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