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Semin Liver Dis 2018; 38(01): 073-086
DOI: 10.1055/s-0038-1629924
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Receptor Interacting Protein Kinases in the Liver

Lily Dara
1   Research Center for Liver Disease, University of Southern California, Keck School of Medicine, Los Angeles, California
2   Division of GI/Liver, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California
› Author Affiliations
Further Information

Publication History

Publication Date:
22 February 2018 (online)

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Abstract

The receptor interacting serine/threonine kinase1 and 3 (RIPK1, RIPK3) are regulators of cell death and survival. RIPK1 kinase activity is required for necroptosis and apoptosis, while its scaffolding function is necessary for survival. Although both proteins can mediate apoptosis, RIPK1 and RIPK3 are most well-known for their role in the execution of necroptosis via the mixed lineage domain like pseudokinase. Necroptosis is a caspase-independent regulated cell death program which was first described in cultured cells with unknown physiologic relevance in the liver. Many recent reports have suggested that RIPK1 and/or RIPK3 participate in liver disease pathogenesis and cell death. Notably, both proteins have been shown to mediate inflammation independent of cell death. Whether necroptosis occurs in hepatocytes, and how it is executed in the presence of an intact caspase machinery is controversial. In spite of this controversy, it is evident that RIPK1 and RIPK3 participate in many experimental liver disease models. Therefore, in addition to cell death signaling, their necroptosis-independent role warrants further examination.

Keywords

RIPK1 - RIPK3 - cell death - necroptosis - apoptosis

Financial Support

This work was supported by NIH grant K08DK109141(LD).


 

  • References

  • 1 Zhang D, Lin J, Han J. Receptor-interacting protein (RIP) kinase family. Cell Mol Immunol 2010; 7 (04) 243-249
    CrossrefPubMedSearch in Google Scholar
  • 2 Meylan E, Burns K, Hofmann K. , et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol 2004; 5 (05) 503-507
    CrossrefPubMedSearch in Google Scholar
  • 3 Kaiser WJ, Daley-Bauer LP, Thapa RJ. , et al. RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. Proc Natl Acad Sci U S A 2014; 111 (21) 7753-7758
    CrossrefPubMedSearch in Google Scholar
  • 4 Polykratis A, Hermance N, Zelic M. , et al. Cutting edge: RIPK1 kinase inactive mice are viable and protected from TNF-induced necroptosis in vivo. J Immunol 2014; 193 (04) 1539-1543
    CrossrefPubMedSearch in Google Scholar
  • 5 Newton K, Dugger DL, Wickliffe KE. , et al. Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis. Science 2014; 343 (6177): 1357-1360
    CrossrefPubMedSearch in Google Scholar
  • 6 Hasegawa M, Fujimoto Y, Lucas PC. , et al. A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J 2008; 27 (02) 373-383
    CrossrefPubMedSearch in Google Scholar
  • 7 Sun X, Lee J, Navas T, Baldwin DT, Stewart TA, Dixit VM. RIP3, a novel apoptosis-inducing kinase. J Biol Chem 1999; 274 (24) 16871-16875
    CrossrefPubMedSearch in Google Scholar
  • 8 Rosenbusch KE, Kortholt A. Activation mechanism of LRRK2 and its cellular functions in Parkinson's disease. Parkinsons Dis 2016; 2016: 7351985
    PubMedSearch in Google Scholar
  • 9 Bae JR, Lee BD. Function and dysfunction of leucine-rich repeat kinase 2 (LRRK2): Parkinson's disease and beyond. BMB Rep 2015; 48 (05) 243-248
    CrossrefPubMedSearch in Google Scholar
  • 10 Stanger BZ, Leder P, Lee TH, Kim E, Seed B. RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 1995; 81 (04) 513-523
    CrossrefPubMedSearch in Google Scholar
  • 11 Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ, Leder P. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity 1998; 8 (03) 297-303
    CrossrefPubMedSearch in Google Scholar
  • 12 Lee TH, Shank J, Cusson N, Kelliher MA. The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J Biol Chem 2004; 279 (32) 33185-33191
    CrossrefPubMedSearch in Google Scholar
  • 13 Kasof GM, Prosser JC, Liu D, Lorenzi MV, Gomes BC. The RIP-like kinase, RIP3, induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria. FEBS Lett 2000; 473 (03) 285-291
    CrossrefPubMedSearch in Google Scholar
  • 14 Dara L, Liu ZX, Kaplowitz N. Questions and controversies: the role of necroptosis in liver disease. Cell Death Dis 2016; 2: 16089
    CrossrefPubMedSearch in Google Scholar
  • 15 Newton K, Sun X, Dixit VM. Kinase RIP3 is dispensable for normal NF-kappa Bs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4. Mol Cell Biol 2004; 24 (04) 1464-1469
    CrossrefPubMedSearch in Google Scholar
  • 16 He S, Wang L, Miao L. , et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 2009; 137 (06) 1100-1111
    CrossrefPubMedSearch in Google Scholar
  • 17 Newton K. RIPK1 and RIPK3: critical regulators of inflammation and cell death. Trends Cell Biol 2015; 25 (06) 347-353
    CrossrefPubMedSearch in Google Scholar
  • 18 Vercammen D, Beyaert R, Denecker G. , et al. Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J Exp Med 1998; 187 (09) 1477-1485
    CrossrefPubMedSearch in Google Scholar
  • 19 He S, Liang Y, Shao F, Wang X. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci U S A 2011; 108 (50) 20054-20059
    CrossrefPubMedSearch in Google Scholar
  • 20 Thapa RJ, Nogusa S, Chen P. , et al. Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proc Natl Acad Sci U S A 2013; 110 (33) E3109-E3118
    CrossrefPubMedSearch in Google Scholar
  • 21 Saveljeva S, Mc Laughlin SL, Vandenabeele P, Samali A, Bertrand MJ. Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells. Cell Death Dis 2015; 6: e1587
    CrossrefPubMedSearch in Google Scholar
  • 22 Guicciardi ME, Malhi H, Mott JL, Gores GJ. Apoptosis and necrosis in the liver. Compr Physiol 2013; 3 (02) 977-1010
    Search in Google Scholar
  • 23 Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003; 114 (02) 181-190
    CrossrefPubMedSearch in Google Scholar
  • 24 Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways. Cell 2008; 133 (04) 693-703
    CrossrefPubMedSearch in Google Scholar
  • 25 Silke J, Rickard JA, Gerlic M. The diverse role of RIP kinases in necroptosis and inflammation. Nat Immunol 2015; 16 (07) 689-697
    CrossrefPubMedSearch in Google Scholar
  • 26 Yuasa T, Ohno S, Kehrl JH, Kyriakis JM. Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. J Biol Chem 1998; 273 (35) 22681-22692
    CrossrefPubMedSearch in Google Scholar
  • 27 Geng J, Ito Y, Shi L. , et al. Regulation of RIPK1 activation by TAK1-mediated phosphorylation dictates apoptosis and necroptosis. Nat Commun 2017; 8 (01) 359
    CrossrefPubMedSearch in Google Scholar
  • 28 Menon MB, Gropengießer J, Fischer J. , et al. p38MAPK/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection. Nat Cell Biol 2017; 19 (10) 1248-1259
    CrossrefPubMedSearch in Google Scholar
  • 29 Jaco I, Annibaldi A, Lalaoui N. , et al. MK2 phosphorylates RIPK1 to prevent TNF-induced cell death. Mol Cell 2017; 66 (05) 698-710.e5
    CrossrefPubMedSearch in Google Scholar
  • 30 Dondelinger Y, Delanghe T, Rojas-Rivera D. , et al. MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. Nat Cell Biol 2017; 19 (10) 1237-1247
    CrossrefPubMedSearch in Google Scholar
  • 31 Dondelinger Y, Jouan-Lanhouet S, Divert T. , et al. NF-κB-independent role of IKKα/IKKβ in preventing RIPK1 kinase-dependent apoptotic and necroptotic cell death during TNF signaling. Mol Cell 2015; 60 (01) 63-76
    CrossrefPubMedSearch in Google Scholar
  • 32 Oberst A. MK2 balances inflammation and cell death. Nat Cell Biol 2017; 19 (10) 1150-1152
    CrossrefPubMedSearch in Google Scholar
  • 33 Feoktistova M, Geserick P, Kellert B. , et al. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms. Mol Cell 2011; 43 (03) 449-463
    CrossrefPubMedSearch in Google Scholar
  • 34 Tenev T, Bianchi K, Darding M. , et al. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell 2011; 43 (03) 432-448
    CrossrefPubMedSearch in Google Scholar
  • 35 Dondelinger Y, Aguileta MA, Goossens V. , et al. RIPK3 contributes to TNFR1-mediated RIPK1 kinase-dependent apoptosis in conditions of cIAP1/2 depletion or TAK1 kinase inhibition. Cell Death Differ 2013; 20 (10) 1381-1392
    CrossrefPubMedSearch in Google Scholar
  • 36 Degterev A, Zhou W, Maki JL, Yuan J. Assays for necroptosis and activity of RIP kinases. Methods Enzymol 2014; 545: 1-33
    PubMedSearch in Google Scholar
  • 37 Mandal P, Berger SB, Pillay S. , et al. RIP3 induces apoptosis independent of pronecrotic kinase activity. Mol Cell 2014; 56 (04) 481-495
    CrossrefPubMedSearch in Google Scholar
  • 38 Newton K, Manning G. Necroptosis and inflammation. Annu Rev Biochem 2016; 85: 743-763
    CrossrefPubMedSearch in Google Scholar
  • 39 Holler N, Zaru R, Micheau O. , et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 2000; 1 (06) 489-495
    CrossrefPubMedSearch in Google Scholar
  • 40 Vercammen D, Brouckaert G, Denecker G. , et al. Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways. J Exp Med 1998; 188 (05) 919-930
    CrossrefPubMedSearch in Google Scholar
  • 41 Degterev A, Hitomi J, Germscheid M. , et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 2008; 4 (05) 313-321
    CrossrefPubMedSearch in Google Scholar
  • 42 Degterev A, Huang Z, Boyce M. , et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 2005; 1 (02) 112-119
    CrossrefPubMedSearch in Google Scholar
  • 43 Sun L, Wang H, Wang Z. , et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 2012; 148 (1-2): 213-227
    CrossrefPubMedSearch in Google Scholar
  • 44 Upton JW, Kaiser WJ, Mocarski ES. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe 2012; 11 (03) 290-297
    CrossrefPubMedSearch in Google Scholar
  • 45 Mocarski ES, Upton JW, Kaiser WJ. Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways. Nat Rev Immunol 2011; 12 (02) 79-88
    CrossrefPubMedSearch in Google Scholar
  • 46 Wang X, Li Y, Liu S. , et al. Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense. Proc Natl Acad Sci U S A 2014; 111 (43) 15438-15443
    CrossrefPubMedSearch in Google Scholar
  • 47 Hildebrand JM, Tanzer MC, Lucet IS. , et al. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc Natl Acad Sci U S A 2014; 111 (42) 15072-15077
    CrossrefPubMedSearch in Google Scholar
  • 48 Dondelinger Y, Declercq W, Montessuit S. , et al. MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Reports 2014; 7 (04) 971-981
    CrossrefPubMedSearch in Google Scholar
  • 49 Wang H, Sun L, Su L. , et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell 2014; 54 (01) 133-146
    CrossrefPubMedSearch in Google Scholar
  • 50 Cai Z, Jitkaew S, Zhao J. , et al. Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol 2014; 16 (01) 55-65
    CrossrefPubMedSearch in Google Scholar
  • 51 Zhao J, Jitkaew S, Cai Z. , et al. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci U S A 2012; 109 (14) 5322-5327
    CrossrefPubMedSearch in Google Scholar
  • 52 Murphy JM, Czabotar PE, Hildebrand JM. , et al. The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 2013; 39 (03) 443-453
    CrossrefPubMedSearch in Google Scholar
  • 53 Grootjans S, Vanden Berghe T, Vandenabeele P. Initiation and execution mechanisms of necroptosis: an overview. Cell Death Differ 2017; 24 (07) 1184-1195
    CrossrefPubMedSearch in Google Scholar
  • 54 Takahashi N, Vereecke L, Bertrand MJ. , et al. RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. Nature 2014; 513 (7516): 95-99
    CrossrefPubMedSearch in Google Scholar
  • 55 Dannappel M, Vlantis K, Kumari S. , et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 2014; 513 (7516): 90-94
    CrossrefPubMedSearch in Google Scholar
  • 56 Moriwaki K, Chan FK. Necroptosis-independent signaling by the RIP kinases in inflammation. Cell Mol Life Sci 2016; 73 (11-12): 2325-2334
    CrossrefPubMedSearch in Google Scholar
  • 57 Suda J, Dara L, Yang L. , et al. Knockdown of RIPK1 markedly exacerbates murine immune-mediated liver injury through massive apoptosis of hepatocytes, independent of necroptosis and inhibition of NF-κB. J Immunol 2016; 197 (08) 3120-3129
    CrossrefPubMedSearch in Google Scholar
  • 58 Wong WW, Gentle IE, Nachbur U, Anderton H, Vaux DL, Silke J. RIPK1 is not essential for TNFR1-induced activation of NF-kappaB. Cell Death Differ 2010; 17 (03) 482-487
    CrossrefPubMedSearch in Google Scholar
  • 59 Van TM, Polykratis A, Straub BK, Kondylis V, Papadopoulou N, Pasparakis M. Kinase-independent functions of RIPK1 regulate hepatocyte survival and liver carcinogenesis. J Clin Invest 2017; 127 (07) 2662-2677
    CrossrefPubMedSearch in Google Scholar
  • 60 Rajput A, Kovalenko A, Bogdanov K. , et al. RIG-I RNA helicase activation of IRF3 transcription factor is negatively regulated by caspase-8-mediated cleavage of the RIP1 protein. Immunity 2011; 34 (03) 340-351
    CrossrefPubMedSearch in Google Scholar
  • 61 Moriwaki K, Bertin J, Gough PJ, Chan FKA. A RIPK3-caspase 8 complex mediates atypical pro-IL-1β processing. J Immunol 2015; 194 (04) 1938-1944
    CrossrefPubMedSearch in Google Scholar
  • 62 Lawlor KE, Khan N, Mildenhall A. , et al. RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat Commun 2015; 6: 6282
    CrossrefPubMedSearch in Google Scholar
  • 63 Newton K, Dugger DL, Maltzman A. , et al. RIPK3 deficiency or catalytically inactive RIPK1 provides greater benefit than MLKL deficiency in mouse models of inflammation and tissue injury. Cell Death Differ 2016; 23 (09) 1565-1576
    CrossrefPubMedSearch in Google Scholar
  • 64 Kang YJ, Bang BR, Han KH. , et al. Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling. Nat Commun 2015; 6: 8371
    CrossrefPubMedSearch in Google Scholar
  • 65 Wong WW, Vince JE, Lalaoui N. , et al. cIAPs and XIAP regulate myelopoiesis through cytokine production in an RIPK1- and RIPK3-dependent manner. Blood 2014; 123 (16) 2562-2572
    CrossrefPubMedSearch in Google Scholar
  • 66 Vince JE, Wong WW, Gentle I. , et al. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity 2012; 36 (02) 215-227
    CrossrefPubMedSearch in Google Scholar
  • 67 Yabal M, Müller N, Adler H. , et al. XIAP restricts TNF- and RIP3-dependent cell death and inflammasome activation. Cell Reports 2014; 7 (06) 1796-1808
    CrossrefPubMedSearch in Google Scholar
  • 68 Kang S, Fernandes-Alnemri T, Rogers C. , et al. Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3. Nat Commun 2015; 6: 7515
    CrossrefPubMedSearch in Google Scholar
  • 69 Gaidt MM, Ebert TS, Chauhan D. , et al. Human monocytes engage an alternative inflammasome pathway. Immunity 2016; 44 (04) 833-846
    CrossrefPubMedSearch in Google Scholar
  • 70 Wree A, Eguchi A, McGeough MD. , et al. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology 2014; 59 (03) 898-910
    CrossrefPubMedSearch in Google Scholar
  • 71 He Y, Hara H, Núñez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 2016; 41 (12) 1012-1021
    CrossrefPubMedSearch in Google Scholar
  • 72 Szabo G, Petrasek J. Inflammasome activation and function in liver disease. Nat Rev Gastroenterol Hepatol 2015; 12 (07) 387-400
    CrossrefPubMedSearch in Google Scholar
  • 73 Guicciardi ME, Gores GJ. Life and death by death receptors. FASEB J 2009; 23 (06) 1625-1637
    CrossrefPubMedSearch in Google Scholar
  • 74 Iorga A, Dara L, Kaplowitz N. Drug-induced liver injury: cascade of events leading to cell death, apoptosis or necrosis. Int J Mol Sci 2017; 18 (05) E1018
    CrossrefPubMedSearch in Google Scholar
  • 75 Hirsova P, Gores GJ. Death receptor-mediated cell death and proinflammatory signaling in nonalcoholic steatohepatitis. Cell Mol Gastroenterol Hepatol 2015; 1 (01) 17-27
    CrossrefPubMedSearch in Google Scholar
  • 76 Ding WX, Yin XM. Dissection of the multiple mechanisms of TNF-alpha-induced apoptosis in liver injury. J Cell Mol Med 2004; 8 (04) 445-454
    CrossrefPubMedSearch in Google Scholar
  • 77 Luedde T, Kaplowitz N, Schwabe RF. Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology 2014; 147 (04) 765-783.e4
    CrossrefPubMedSearch in Google Scholar
  • 78 Dara L, Johnson H, Suda J. , et al. Receptor interacting protein kinase 1 mediates murine acetaminophen toxicity independent of the necrosome and not through necroptosis. Hepatology 2015; 62 (06) 1847-1857
    CrossrefPubMedSearch in Google Scholar
  • 79 Günther C, He GW, Kremer AE. , et al. The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis. J Clin Invest 2016; 126 (11) 4346-4360
    CrossrefPubMedSearch in Google Scholar
  • 80 Dara L, Liu ZX, Kaplowitz N. A murder mystery in the liver: who done it and how?. J Clin Invest 2016; 126 (11) 4068-4071
    CrossrefPubMedSearch in Google Scholar
  • 81 Wang S, Ni HM, Dorko K. , et al. Increased hepatic receptor interacting protein kinase 3 expression due to impaired proteasomal functions contributes to alcohol-induced steatosis and liver injury. Oncotarget 2016; 7 (14) 17681-17698
    PubMedSearch in Google Scholar
  • 82 Roychowdhury S, McCullough RL, Sanz-Garcia C. , et al. Receptor interacting protein 3 protects mice from high-fat diet-induced liver injury. Hepatology 2016; 64 (05) 1518-1533
    CrossrefPubMedSearch in Google Scholar
  • 83 Roychowdhury S, McMullen MR, Pisano SG, Liu X, Nagy LE. Absence of receptor interacting protein kinase 3 prevents ethanol-induced liver injury. Hepatology 2013; 57 (05) 1773-1783
    CrossrefPubMedSearch in Google Scholar
  • 84 Gautheron J, Vucur M, Reisinger F. , et al. A positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis. EMBO Mol Med 2014; 6 (08) 1062-1074
    CrossrefPubMedSearch in Google Scholar
  • 85 Afonso MB, Rodrigues PM, Carvalho T. , et al. Necroptosis is a key pathogenic event in human and experimental murine models of non-alcoholic steatohepatitis. Clin Sci (Lond) 2015; 129 (08) 721-739
    CrossrefPubMedSearch in Google Scholar
  • 86 An J, Mehrhof F, Harms C. , et al. ARC is a novel therapeutic approach against acetaminophen-induced hepatocellular necrosis. J Hepatol 2013; 58 (02) 297-305
    CrossrefPubMedSearch in Google Scholar
  • 87 Deutsch M, Graffeo CS, Rokosh R. , et al. Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury. Cell Death Dis 2015; 6: e1759
    CrossrefPubMedSearch in Google Scholar
  • 88 Ramachandran A, McGill MR, Xie Y, Ni HM, Ding WX, Jaeschke H. Receptor interacting protein kinase 3 is a critical early mediator of acetaminophen-induced hepatocyte necrosis in mice. Hepatology 2013; 58 (06) 2099-2108
    CrossrefPubMedSearch in Google Scholar
  • 89 Takemoto K, Hatano E, Iwaisako K. , et al. Necrostatin-1 protects against reactive oxygen species (ROS)-induced hepatotoxicity in acetaminophen-induced acute liver failure. FEBS Open Bio 2014; 4: 777-787
    CrossrefPubMedSearch in Google Scholar
  • 90 Zhang YF, He W, Zhang C. , et al. Role of receptor interacting protein (RIP)1 on apoptosis-inducing factor-mediated necroptosis during acetaminophen-evoked acute liver failure in mice. Toxicol Lett 2014; 225 (03) 445-453
    CrossrefPubMedSearch in Google Scholar
  • 91 Takahashi N, Duprez L, Grootjans S. , et al. Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models. Cell Death Dis 2012; 3: e437
    CrossrefPubMedSearch in Google Scholar
  • 92 Schneider AT, Gautheron J, Tacke F, Vucur M, Luedde T. Receptor interacting protein kinase-1 (RIPK1) in hepatocytes does not mediate murine acetaminophen toxicity. Hepatology 2016; 64 (01) 306-308
    PubMedSearch in Google Scholar
  • 93 Heymann F, Hamesch K, Weiskirchen R, Tacke F. The concanavalin A model of acute hepatitis in mice. Lab Anim 2015; 49 (1, Suppl): 12-20
    CrossrefPubMedSearch in Google Scholar
  • 94 Leist M, Gantner F, Bohlinger I, Tiegs G, Germann PG, Wendel A. Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. Am J Pathol 1995; 146 (05) 1220-1234
    PubMedSearch in Google Scholar
  • 95 Mizuhara H, O'Neill E, Seki N. , et al. T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. J Exp Med 1994; 179 (05) 1529-1537
    CrossrefPubMedSearch in Google Scholar
  • 96 Trautwein C, Rakemann T, Brenner DA. , et al. Concanavalin A-induced liver cell damage: activation of intracellular pathways triggered by tumor necrosis factor in mice. Gastroenterology 1998; 114 (05) 1035-1045
    CrossrefPubMedSearch in Google Scholar
  • 97 Jouan-Lanhouet S, Arshad MI, Piquet-Pellorce C. , et al. TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation. Cell Death Differ 2012; 19 (12) 2003-2014
    CrossrefPubMedSearch in Google Scholar
  • 98 Arshad MI, Piquet-Pellorce C, Filliol A. , et al. The chemical inhibitors of cellular death, PJ34 and necrostatin-1, down-regulate IL-33 expression in liver. J Mol Med (Berl) 2015; 93 (08) 867-878
    CrossrefPubMedSearch in Google Scholar
  • 99 Zhou Y, Dai W, Lin C. , et al. Protective effects of necrostatin-1 against concanavalin A-induced acute hepatic injury in mice. Mediators Inflamm 2013; 2013: 706156
    PubMedSearch in Google Scholar
  • 100 Filliol A, Piquet-Pellorce C, Le Seyec J. , et al. RIPK1 protects from TNF-α-mediated liver damage during hepatitis. Cell Death Dis 2016; 7 (11) e2462
    CrossrefPubMedSearch in Google Scholar
  • 101 Weinlich R, Oberst A, Dillon CP. , et al. Protective roles for caspase-8 and cFLIP in adult homeostasis. Cell Reports 2013; 5 (02) 340-348
    CrossrefPubMedSearch in Google Scholar
  • 102 Filliol A, Piquet-Pellorce C, Raguénès-Nicol C. , et al. RIPK1 protects hepatocytes from Kupffer cells-mediated TNF-induced apoptosis in mouse models of PAMP-induced hepatitis. J Hepatol 2017; 66 (06) 1205-1213
    CrossrefPubMedSearch in Google Scholar
  • 103 Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science 2011; 332 (6037): 1519-1523
    CrossrefPubMedSearch in Google Scholar
  • 104 Louvet A, Mathurin P. Alcoholic liver disease: mechanisms of injury and targeted treatment. Nat Rev Gastroenterol Hepatol 2015; 12 (04) 231-242
    CrossrefPubMedSearch in Google Scholar
  • 105 Feldstein AE, Canbay A, Angulo P. , et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003; 125 (02) 437-443
    CrossrefPubMedSearch in Google Scholar
  • 106 Hirsova P, Gores GJ. Reply. Cell Mol Gastroenterol Hepatol 2015; 1 (03) 265-266
    PubMedSearch in Google Scholar
  • 107 Hatting M, Zhao G, Schumacher F. , et al. Hepatocyte caspase-8 is an essential modulator of steatohepatitis in rodents. Hepatology 2013; 57 (06) 2189-2201
    CrossrefPubMedSearch in Google Scholar
  • 108 Witek RP, Stone WC, Karaca FG. , et al. Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis. Hepatology 2009; 50 (05) 1421-1430
    CrossrefPubMedSearch in Google Scholar
  • 109 Santhekadur PK, Kumar DP, Sanyal AJ. Preclinical models of non-alcoholic fatty liver disease. J Hepatol 2017; S0168-8278(17)32422-4
    PubMedSearch in Google Scholar
  • 110 Gautheron J, Vucur M, Luedde T. Necroptosis in nonalcoholic steatohepatitis. Cell Mol Gastroenterol Hepatol 2015; 1 (03) 264-265
    PubMedSearch in Google Scholar
  • 111 Hao F, Cubero FJ, Ramadori P. , et al. Inhibition of Caspase-8 does not protect from alcohol-induced liver apoptosis but alleviates alcoholic hepatic steatosis in mice. Cell Death Dis 2017; 8 (10) e3152
    CrossrefPubMedSearch in Google Scholar
  • 112 Schneider AT, Gautheron J, Feoktistova M. , et al. RIPK1 suppresses a TRAF2-dependent pathway to liver cancer. Cancer Cell 2017; 31 (01) 94-109
    CrossrefPubMedSearch in Google Scholar
  • 113 Kondylis V, Polykratis A, Ehlken H. , et al. NEMO prevents steatohepatitis and hepatocellular carcinoma by inhibiting RIPK1 kinase activity-mediated hepatocyte apoptosis. Cancer Cell 2015; 28 (05) 582-598
    CrossrefPubMedSearch in Google Scholar
  • 114 Sun J, Yu X, Wang C. , et al. RIP-1/c-FLIPL induce hepatic cancer cell apoptosis through regulating tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Med Sci Monit 2017; 23: 1190-1199
    CrossrefPubMedSearch in Google Scholar
  • 115 Koppe C, Verheugd P, Gautheron J. , et al. IκB kinaseα/β control biliary homeostasis and hepatocarcinogenesis in mice by phosphorylating the cell-death mediator receptor-interacting protein kinase 1. Hepatology 2016; 64 (04) 1217-1231
    CrossrefPubMedSearch in Google Scholar
  • 116 Vucur M, Reisinger F, Gautheron J. , et al. RIP3 inhibits inflammatory hepatocarcinogenesis but promotes cholestasis by controlling caspase-8- and JNK-dependent compensatory cell proliferation. Cell Reports 2013; 4 (04) 776-790
    CrossrefPubMedSearch in Google Scholar
  • 117 Luedde T, Beraza N, Kotsikoris V. , et al. Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 2007; 11 (02) 119-132
    CrossrefPubMedSearch in Google Scholar
  • 118 Wang C, Yao B, Xu M, Zheng X. RIP1 upregulation promoted tumor progression by activating AKT/Bcl-2/BAX signaling and predicted poor postsurgical prognosis in HCC. Tumour Biol 2016; 37 (11) 15305-15313
    CrossrefPubMedSearch in Google Scholar
  • 119 Afonso MB, Rodrigues PM, Simão AL. , et al. Activation of necroptosis in human and experimental cholestasis. Cell Death Dis 2016; 7 (09) e2390
    CrossrefPubMedSearch in Google Scholar
  • 120 Rehermann B. Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells. Nat Med 2013; 19 (07) 859-868
    CrossrefPubMedSearch in Google Scholar
  • 121 Mundt B, Kühnel F, Zender L. , et al. Involvement of TRAIL and its receptors in viral hepatitis. FASEB J 2003; 17 (01) 94-96
    CrossrefPubMedSearch in Google Scholar
  • 122 Song H, Binh VQ, Duy DN. , et al. Variations in the serum concentrations of soluble Fas and soluble Fas ligand in Vietnamese patients infected with hepatitis B virus. J Med Virol 2004; 73 (02) 244-249
    CrossrefPubMedSearch in Google Scholar
  • 123 Streetz K, Leifeld L, Grundmann D. , et al. Tumor necrosis factor alpha in the pathogenesis of human and murine fulminant hepatic failure. Gastroenterology 2000; 119 (02) 446-460
    CrossrefPubMedSearch in Google Scholar
  • 124 Fang JW, Shen WW, Meager A, Lau JY. Activation of the tumor necrosis factor-alpha system in the liver in chronic hepatitis B virus infection. Am J Gastroenterol 1996; 91 (04) 748-753
    PubMedSearch in Google Scholar
  • 125 Yoon JH, Gores GJ. Death receptor-mediated apoptosis and the liver. J Hepatol 2002; 37 (03) 400-410
    CrossrefPubMedSearch in Google Scholar
  • 126 Lim EJ, El Khobar K, Chin R. , et al. Hepatitis C virus-induced hepatocyte cell death and protection by inhibition of apoptosis. J Gen Virol 2014; 95 (Pt 10): 2204-2215
    CrossrefPubMedSearch in Google Scholar