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Decoding cell death signals in liver inflammation.
J Hepatol. 2013 Sep; 59(3):583-94.JH

Abstract

Inflammation can be either beneficial or detrimental to the liver, depending on multiple factors. Mild (i.e., limited in intensity and destined to resolve) inflammatory responses have indeed been shown to exert consistent hepatoprotective effects, contributing to tissue repair and promoting the re-establishment of homeostasis. Conversely, excessive (i.e., disproportionate in intensity and permanent) inflammation may induce a massive loss of hepatocytes and hence exacerbate the severity of various hepatic conditions, including ischemia-reperfusion injury, systemic metabolic alterations (e.g., obesity, diabetes, non-alcoholic fatty liver disorders), alcoholic hepatitis, intoxication by xenobiotics and infection, de facto being associated with irreversible liver damage, fibrosis, and carcinogenesis. Both liver-resident cells (e.g., Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells) and cells that are recruited in response to injury (e.g., monocytes, macrophages, dendritic cells, natural killer cells) emit pro-inflammatory signals including - but not limited to - cytokines, chemokines, lipid messengers, and reactive oxygen species that contribute to the apoptotic or necrotic demise of hepatocytes. In turn, dying hepatocytes release damage-associated molecular patterns that-upon binding to evolutionary conserved pattern recognition receptors-activate cells of the innate immune system to further stimulate inflammatory responses, hence establishing a highly hepatotoxic feedforward cycle of inflammation and cell death. In this review, we discuss the cellular and molecular mechanisms that account for the most deleterious effect of hepatic inflammation at the cellular level, that is, the initiation of a massive cell death response among hepatocytes.

Authors+Show Affiliations

INSERM, UMRS 769, LabEx LERMIT, F-92290 Châtenay Malabry, France.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23567086

Citation

Brenner, Catherine, et al. "Decoding Cell Death Signals in Liver Inflammation." Journal of Hepatology, vol. 59, no. 3, 2013, pp. 583-94.
Brenner C, Galluzzi L, Kepp O, et al. Decoding cell death signals in liver inflammation. J Hepatol. 2013;59(3):583-94.
Brenner, C., Galluzzi, L., Kepp, O., & Kroemer, G. (2013). Decoding cell death signals in liver inflammation. Journal of Hepatology, 59(3), 583-94. https://doi.org/10.1016/j.jhep.2013.03.033
Brenner C, et al. Decoding Cell Death Signals in Liver Inflammation. J Hepatol. 2013;59(3):583-94. PubMed PMID: 23567086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Decoding cell death signals in liver inflammation. AU - Brenner,Catherine, AU - Galluzzi,Lorenzo, AU - Kepp,Oliver, AU - Kroemer,Guido, Y1 - 2013/04/06/ PY - 2013/02/15/received PY - 2013/03/20/revised PY - 2013/03/27/accepted PY - 2013/4/10/entrez PY - 2013/4/10/pubmed PY - 2014/4/26/medline KW - 5-lipoxygenase activating protein KW - AGER KW - ALOX5 KW - ANT KW - ASK1 KW - ATF6 KW - Apoptosis KW - C/EPB homologous protein KW - CFLAR KW - CHOP KW - COX2 KW - CRT KW - DAMP KW - DAPK1 KW - DCC KW - DIABLO KW - ECP KW - EDN KW - EGFR KW - EIF2AK3 KW - EP KW - ER KW - ERN1 KW - FFA KW - FLAP KW - FPR1 KW - GADD34 KW - GM-CSF KW - GRP78 KW - GSK-3β KW - HBV KW - HCV KW - HFD KW - HMGB1 KW - HSC KW - HSP KW - IFNγ KW - IL KW - IL-1 receptor antagonist KW - IL-1RA KW - IR KW - IRE1α KW - JNK KW - LPS KW - Lipotoxicity KW - MAMP KW - MAPK KW - MBP KW - MLKL KW - MOMP KW - NADPH oxidase KW - NAFLD KW - NASH KW - NK KW - NO KW - NO synthase KW - NOS KW - NOX KW - NSAID KW - Necrosis KW - Non-alcoholic necrosis steatohepatitis KW - PERK KW - PGAM5 KW - PGE KW - PGE receptor 1, subtype EP1 KW - PINK1 KW - PKR-related ER kinase KW - PP1 KW - PRR KW - PTEN-induced putative kinase 1 KW - PTGER1 KW - PTPC KW - Pattern recognition receptors KW - RIPK1 KW - RNS KW - ROS KW - S1P KW - SIGLEC10 KW - SIRS KW - STAT3 KW - TGFβ KW - TLR KW - TNF receptor 1 KW - TNF-related apoptosis inducing ligand KW - TNFR1 KW - TNFα KW - TRAIL KW - Toll-like receptor KW - Tumor necrosis factor receptor KW - UPR KW - VDAC KW - aSMase KW - acidic sphingomyelinase KW - activating transcription factor 6 KW - adenine nucleotide translocase KW - advanced glycosylation end product-specific receptor KW - apoptosis signal-regulating kinase 1 KW - arachidonate 5-lipoxygenase KW - c-Jun N-terminal kinase KW - calreticulin KW - caspase-8 and FADD-like apoptosis regulator KW - cyclooxygenase 2 KW - damage-associated molecular pattern KW - death-associated protein kinase 1 KW - deleted in colorectal carcinoma KW - direct IAP-binding protein with low pI KW - eIF2α KW - eIF2α kinase 3 KW - eNOS KW - endoplasmic reticulum KW - endoplasmic reticulum to nucleus signaling 1 KW - endothelial NOS KW - eosinophil cationic protein KW - eosinophil peroxidase KW - eosinophil-derived neurotoxin KW - epidermal growth factor receptor KW - eukaryotic translation initiation factor 2α KW - formyl peptide receptor 1 KW - free fatty acid KW - glucose-regulated protein, 78kDa KW - glycogen synthase kinase 3β KW - granulocyte macrophage colony stimulating factor KW - growth arrest- and DNA damage-inducible gene 34 KW - heat-shock protein KW - hepatic stellate cell KW - hepatitis B virus KW - hepatitis C virus KW - high mobility group box 1 KW - high-fat diet KW - iNOS KW - inducible NOS KW - inositol-requiring enzyme 1α KW - interferon γ KW - interleukin KW - ischemia/reperfusion KW - lipopolysaccharide KW - major basic protein KW - microbe-associated molecular pattern KW - mitochondrial outer membrane permeabilization KW - mitochondrial transmembrane potential KW - mitogen-activated protein kinase KW - mixed lineage kinase domain-like KW - natural killer KW - nitric oxide KW - non-alcoholic fatty liver disease KW - non-alcoholic steatohepatitis KW - non-steroidal anti-inflammatory drug KW - pattern recognition receptor KW - permeability transition pore complex KW - phosphoglycerate mutase family member 5 KW - prostaglandin E KW - protein phosphatase 1 KW - reactive nitrogen species KW - reactive oxygen species KW - receptor-interacting protein kinase 1 KW - sialic acid-binding Ig-like lectin 10 KW - signal transducer and activator of transcription 3 KW - sphingosine-1-phosphate KW - systemic inflammatory response syndrome KW - transforming growth factor β KW - tumor necrosis factor α KW - unfolded protein response KW - voltage-dependent anion channel KW - Δψ(m) SP - 583 EP - 94 JF - Journal of hepatology JO - J Hepatol VL - 59 IS - 3 N2 - Inflammation can be either beneficial or detrimental to the liver, depending on multiple factors. Mild (i.e., limited in intensity and destined to resolve) inflammatory responses have indeed been shown to exert consistent hepatoprotective effects, contributing to tissue repair and promoting the re-establishment of homeostasis. Conversely, excessive (i.e., disproportionate in intensity and permanent) inflammation may induce a massive loss of hepatocytes and hence exacerbate the severity of various hepatic conditions, including ischemia-reperfusion injury, systemic metabolic alterations (e.g., obesity, diabetes, non-alcoholic fatty liver disorders), alcoholic hepatitis, intoxication by xenobiotics and infection, de facto being associated with irreversible liver damage, fibrosis, and carcinogenesis. Both liver-resident cells (e.g., Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells) and cells that are recruited in response to injury (e.g., monocytes, macrophages, dendritic cells, natural killer cells) emit pro-inflammatory signals including - but not limited to - cytokines, chemokines, lipid messengers, and reactive oxygen species that contribute to the apoptotic or necrotic demise of hepatocytes. In turn, dying hepatocytes release damage-associated molecular patterns that-upon binding to evolutionary conserved pattern recognition receptors-activate cells of the innate immune system to further stimulate inflammatory responses, hence establishing a highly hepatotoxic feedforward cycle of inflammation and cell death. In this review, we discuss the cellular and molecular mechanisms that account for the most deleterious effect of hepatic inflammation at the cellular level, that is, the initiation of a massive cell death response among hepatocytes. SN - 1600-0641 UR - https://www.unboundmedicine.com/medline/citation/23567086/Decoding_cell_death_signals_in_liver_inflammation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(13)00213-4 DB - PRIME DP - Unbound Medicine ER -