Abstract
Tumor necrosis factor-α (TNF) is a pleiotropic cytokine whose biological functions regulate the cellular responses of injury and repair, inflammation and immunity, and proliferation. In the liver, TNF exerts autocrine and paracrine effects that mediate a variety of pathophysiological states that involve liver injury and cell death and/or hepatocellular proliferation. Thus, TNF is a central regulator of hepatic physiology and delineation of the complex signaling pathways that mediate the disparate effects of this cytokine has contributed to our understanding of its function. In particular, investigations have attempted to determine how this factor could promote either cell proliferation or death in hepatocytes under different physiologic circumstances. With these studies has come an increased understanding of the complex events that determine whether a hepatocyte undergoes apoptosis or proliferation following TNF stimulation. This chapter will focus initially on signaling events that follow TNF ligand–receptor interaction, and subsequently on the precise functions of TNF signaling in specific pathophysiologic states. Although considerable progress has been made in defining TNF signaling pathways in hepatocytes, the challenge remains to determine how these signal cascades regulate disease states in order to manipulate these pathways for the treatment of human liver diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Kern PA, Ranganathan S, Li C et al (2001) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280:E745–E751
Loffreda S, Rai R, Yang SQ et al (1997) Bile ducts and portal and central veins are major producers of tumor necrosis factor α in regenerating rat liver. Gastroenterology 112:2089–2098
Vandenabeele P, Declercq R, Beyaert W, Fiers W (1988) Two tumor necrosis factor receptors: structure and function. Trends Cell Biol 5:392–399
Banner DW, D’Arcy A, Janes W et al (1993) Crystal structure of the soluble human 55 kd TNF receptor-human TNF β complex: implications for TNF receptor activation. Cell 73: 431–445
Black RA, Rauch CT, Kozlosky CJ et al (1997) A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells. Nature 385:729–733
Moss ML, Lambert MH (2002) Shedding of membrane proteins by ADAM family proteases. Essays Biochem 38: 141–153
Amour A, Slocombe PM, Webster A et al (1998) TNF-α converting enzyme (TACE) is inhibited by TIMP-3. FEBS Lett 435:39–44
Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10:45–65
Chan FK, Chun HJ, Zheng L et al (2000) A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288:2351–2354
Wang H, Czura CJ, Tracey KJ (2003) Tumor necrosis factor. In: Thomson AW, Lotze MT (eds) The Cytokine Handbook, 4th edn. Academic, Amsterdam, pp 837–860
Grell M, Douni E, Wajant H et al (1995) The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 83: 793–802
Aggarwal BB (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3:745–756
Kresse M, Latta M, Kunstle G et al (2005) Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors. J Immunol 175:4076–4083
Hehlgans T, Seitz C, Lewis C, Mannel DN (2001) Hypoxic upregulation of TNF receptor type 2 expression involves NF-IL-6 and is independent of HIF-1 or HIF-2. J Interferon Cytokine Res 21:757–762
Grell M, Wajant H, Zimmermann G, Scheurich P (1998) The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor. PNAS 95:570–575
Barbara JA, Smith WB, Gamble JR et al (1994) Dissociation of TNF-α cytotoxic and proinflammatory activities by p55 receptor and p75 receptor-selective TNF-α mutants. EMBO J 13:843–850
Tartaglia LA, Pennica D, Goeddel DV (1993) Ligand passing: the 75-kDa tumor necrosis factor (TNF) receptor recruits TNF for signaling by the 55-kDa TNF receptor. J Biol Chem 268:18542–18548
Fotin-Mleczek M, Henkler F, Samel D et al (2002) Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8. J Cell Sci 115:2757–2770
Depuydt B, van Loo G, Vandenabeele P, Declercq W (2005) Induction of apoptosis by TNF receptor 2 in a T-cell hybridoma is FADD dependent and blocked by caspase-8 inhibitors. J Cell Sci 118:497–504
Masli S, Turpie B (2008) Anti-inflammatory effects of tumour necrosis factor (TNF)-α are mediated via TNF-R2 (p75) in tolerogenic transforming growth factor-β-treated antigen-presenting cells. Immunology 127:62–72
Baumel M, Lechner A, Hehlgans T, Mannel DN (2008) Enhanced susceptibility to Con A-induced liver injury in mice transgenic for the intracellular isoform of human TNF receptor type 2. J Leukoc Biol 84:162–169
Bradley JR (2008) TNF-mediated inflammatory disease. J Pathol 214:149–160
Peschon JJ, Slack JL, Reddy P et al (1998) An essential role for ectodomain shedding in mammalian development. Science 282:1281–1284
Streetz K, Leifeld L, Grundmann D et al (2000) Tumor necrosis factor α in the pathogenesis of human and murine fulminant hepatic failure. Gastroenterology 119:446–460
Volpes R, van den Oord JJ, De Vos R, Desmet VJ (1992) Hepatic expression of type A and type B receptors for tumor necrosis factor. J Hepatol 14:361–369
Czaja MJ, Xu J, Alt E (1995) Prevention of carbon tetrachloride-induced rat liver injury by soluble tumor necrosis factor receptor. Gastroenterology 108:1849–1854
Legler DF, Micheau O, Doucey MA et al (2003) Recruitment of TNF receptor 1 to lipid rafts is essential for TNFα-mediated NF-κB activation. Immunity 18:655–664
Ashkenazi A, Dixit VM (1999) Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11:255–260
Hsu H, Shu HB, Pan MG, Goeddel DV (1996) TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299–308
Peter ME, Krammer PH (2003) The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 10:26–35
Bhardwaj A, Aggarwal BB (2003) Receptor-mediated choreography of life and death. J Clin Immunol 23:317–332
Hsu H, Xiong J, Goeddel DV (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation. Cell 81:495–504
Jiang Y, Woronicz JD, Liu W, Goeddel DV (1999) Prevention of constitutive TNF receptor 1 signaling by silencer of death domains. Science 283:543–546
Chinnaiyan AM, Tepper CG, Seldin MF et al (1996) FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem 271:4961–4965
Chinnaiyan AM, O’Rourke K, Tewari M, Dixit VM (1995) FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 81: 505–512
Ermolaeva MA, Michallet MC, Papadopoulou N et al (2008) Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nat Immunol 9:1037–1046
Tibbetts MD, Zheng L, Lenardo MJ (2003) The death effector domain protein family: regulators of cellular homeostasis. Nat Immunol 4:404–409
Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316
Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383–424
Kischkel FC, Hellbardt S, Behrmann I et al (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. EMBO J 14:5579–5588
Muzio M, Stockwell BR, Stennicke HR et al (1998) An induced proximity model for caspase-8 activation. J Biol Chem 273:2926–2930
Juo P, Kuo CJ, Yuan J, Blenis J (1998) Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Curr Biol 8:1001–1008
Micheau O, Tschopp J (2003) Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114:181–190
Yeh WC, Itie A, Elia AJ et al (2000) Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. Immunity 12:633–642
Harper N, Hughes M, MacFarlane M, Cohen GM (2003) Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis. J Biol Chem 278:25534–25541
Bradham CA, Qian T, Streetz K et al (1998) The mitochondrial permeability transition is required for tumor necrosis factor α-mediated apoptosis and cytochrome c release. Mol Cell Biol 18:6353–6364
Barnhart BC, Alappat EC, Peter ME (2003) The CD95 type I/ type II model. Semin Immunol 15:185–193
Wei MC, Zong WX, Cheng EH et al (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727–730
Zhao Y, Ding WX, Qian T et al (2003) Bid activates multiple mitochondrial apoptotic mechanisms in primary hepatocytes after death receptor engagement. Gastroenterology 125: 854–867
Zhao Y, Li S, Childs EE et al (2001) Activation of pro-death Bcl-2 family proteins and mitochondria apoptosis pathway in tumor necrosis factor-α-induced liver injury. J Biol Chem 276:27432–27440
Chen X, Ding WX, Ni HM et al (2007) Bid-independent mitochondrial activation in tumor necrosis factor α-induced apoptosis and liver injury. Mol Cell Biol 27:541–553
Zou H, Li Y, Liu X, Wang X (1999) An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274:11549–11556
Scaffidi C, Fulda S, Srinivasan A et al (1998) Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17:1675–1687
de la Coste A, Fabre M, McDonell N et al (1999) Differential protective effects of Bcl-xL and Bcl-2 on apoptotic liver injury in transgenic mice. Am J Physiol 277:G702–G708
Van Molle W, Denecker G, Rodriguez I et al (1999) Activation of caspases in lethal experimental hepatitis and prevention by acute phase proteins. J Immunol 163:5235–5241
Deng Y, Ren X, Yang L et al (2003) A JNK-dependent pathway is required for TNFα-induced apoptosis. Cell 115:61–70
Guicciardi ME, Deussing J, Miyoshi H et al (2000) Cathepsin B contributes to TNF-α-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J Clin Invest 106:1127–1137
Werneburg N, Guicciardi ME, Yin XM, Gores GJ (2004) TNF-α-mediated lysosomal permeabilization is FAN and caspase 8/Bid dependent. Am J Physiol Gastrointest Liver Physiol 287:G436–G443
Werneburg NW, Guicciardi ME, Bronk SF, Gores GJ (2002) Tumor necrosis factor-α-associated lysosomal permeabilization is cathepsin B dependent. Am J Physiol Gastrointest Liver Physiol 283:G947–G956
Li S, Zhao Y, He X et al (2002) Relief of extrinsic pathway inhibition by the Bid-dependent mitochondrial release of Smac in Fas-mediated hepatocyte apoptosis. J Biol Chem 277:26912–26920
Jones BE, Lo CR, Liu H et al (2000) Hepatocytes sensitized to tumor necrosis factor-α cytotoxicity undergo apoptosis through caspase-dependent and caspase-independent pathways. J Biol Chem 275:705–712
Kunstle G, Hentze H, Germann PG et al (1999) Concanavalin A hepatotoxicity in mice: tumor necrosis factor-mediated organ failure independent of caspase-3-like protease activation. Hepatology 30:1241–1251
Liu H, Jones BE, Bradham C, Czaja MJ (2002) Increased cytochrome P-450 2E1 expression sensitizes hepatocytes to c-Jun-mediated cell death from TNF-α. Am J Physiol Gastrointest Liver Physiol 282:G257–G266
Moorthy AK, Ghosh G (2003) p105-IκBγ and prototypical IκBs use a similar mechanism to bind but a different mechanism to regulate the subcellular localization of NF-κB. J Biol Chem 278:556–566
Solan NJ, Miyoshi H, Carmona EM et al (2002) RelB cellular regulation and transcriptional activity are regulated by p100. J Biol Chem 277:1405–1418
Ghosh S, Karin M (2002) Missing pieces in the NF-κB puzzle. Cell 109:S81–S96
Park YC, Ye H, Hsia C et al (2000) A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell 101:777–787
Park YC, Burkitt V, Villa AR et al (1999) Structural basis for self-association and receptor recognition of human TRAF2. Nature 398:533–538
Tada K, Okazaki T, Sakon S et al (2001) Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-κB activation and protection from cell death. J Biol Chem 276: 36530–36534
Perkins ND (2000) The Rel/NF-κB family: friend and foe. Trends Biochem Sci 25:434–440
Devin A, Cook A, Lin Y et al (2000) The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation. Immunity 12:419–429
Devin A, Lin Y, Yamaoka S et al (2001) The α and β subunits of IκB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF. Mol Cell Biol 21:3986–3994
Neumann M, Grieshammer T, Chuvpilo S et al (1995) RelA/p65 is a molecular target for the immunosuppressive action of protein kinase A. EMBO J 14:1991–2004
Leitges M, Sanz L, Martin P et al (2001) Targeted disruption of the ζPKC gene results in the impairment of the NF-κB pathway. Mol Cell 8:771–780
Oliver FJ, Menissier-de Murcia J, Nacci C et al (1999) Resistance to endotoxic shock as a consequence of defective NF-κB activation in poly (ADP-ribose) polymerase-1 deficient mice. EMBO J 18:4446–4454
Wang D, Westerheide SD, Hanson JL, Baldwin AS Jr (2000) Tumor necrosis factor α-induced phosphorylation of RelA/p65 on Ser529 is controlled by casein kinase II. J Biol Chem 275:32592–32597
Beg AA, Sha WC, Bronson RT et al (1995) Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature 376:167–170
Alcamo E, Mizgerd JP, Horwitz BH et al (2001) Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-κB in leukocyte recruitment. J Immunol 167:1592–1600
Xu Y, Bialik S, Jones BE et al (1998) NF-κB inactivation converts a hepatocyte cell line TNF-α response from proliferation to apoptosis. Am J Physiol 275:C1058–C1066
Osawa Y, Banno Y, Nagaki M et al (2001) TNF-α-induced sphingosine 1-phosphate inhibits apoptosis through a phosphatidylinositol 3-kinase/Akt pathway in human hepatocytes. J Immunol 167:173–180
Hatano E, Brenner DA (2001) Akt protects mouse hepatocytes from TNF-α- and Fas-mediated apoptosis through NK-κB activation. Am J Physiol Gastrointest Liver Physiol 281: G1357–G1368
Li Q, Van Antwerp D, Mercurio F et al (1999) Severe liver degeneration in mice lacking the IκB kinase 2 gene. Science 284:321–325
Rudolph D, Yeh WC, Wakeham A et al (2000) Severe liver degeneration and lack of NF-κB activation in NEMO/IKKγ-deficient mice. Genes Dev 14:854–862
Luedde T, Assmus U, Wustefeld T et al (2005) Deletion of IKK2 in hepatocytes does not sensitize these cells to TNF-induced apoptosis but protects from ischemia/reperfusion injury. J Clin Invest 115:849–859
Beraza N, Ludde T, Assmus U et al (2007) Hepatocyte-specific IKK γ/NEMO expression determines the degree of liver injury. Gastroenterology 132:2504–2517
Leist M, Gantner F, Bohlinger I et al (1994) Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-α requires transcriptional arrest. J Immunol 153:1778–1788
Hatano E, Bennett BL, Manning AM et al (2001) NF-κB stimulates inducible nitric oxide synthase to protect mouse hepatocytes from TNF-α- and Fas-mediated apoptosis. Gastroenterology 120:1251–1262
Liu H, Lo CR, Czaja MJ (2002) NF-κB inhibition sensitizes hepatocytes to TNF-induced apoptosis through a sustained activation of JNK and c-Jun. Hepatology 35:772–778
Czaja MJ (2003) The future of GI and liver research: editorial perspectives. III. JNK/AP-1 regulation of hepatocyte death. Am J Physiol Gastrointest Liver Physiol 284:G875–G879
Chang L, Kamata H, Solinas G et al (2006) The E3 ubiquitin ligase itch couples JNK activation to TNFα-induced cell death by inducing c-FLIP(L) turnover. Cell 124:601–613
De Smaele E, Zazzeroni F, Papa S et al (2001) Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling. Nature 414:308–313
Schwabe RF, Uchinami H, Qian T et al (2004) Differential requirement for c-Jun NH2-terminal kinase in TNFα- and Fas-mediated apoptosis in hepatocytes. FASEB J 18:720–722
Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252
Tuncman G, Hirosumi J, Solinas G et al (2006) Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc Natl Acad Sci U S A 103:10741–10746
Wang Y, Singh R, Lefkowitch JH et al (2006) Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway. J Biol Chem 281:15258–15267
Ni HM, Chen X, Ding WX et al (2008) Differential roles of JNK in ConA/GalN and ConA-induced liver injury in mice. Am J Pathol 173:962–972
Lee TH, Huang Q, Oikemus S et al (2003) The death domain kinase RIP1 is essential for tumor necrosis factor α signaling to p38 mitogen-activated protein kinase. Mol Cell Biol 23:8377–8385
Akerman P, Cote P, Yang SQ et al (1992) Antibodies to tumor necrosis factor-α inhibit liver regeneration after partial hepatectomy. Am J Physiol 263:G579–G585
Yamada Y, Kirillova I, Peschon JJ, Fausto N (1997) Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor. Proc Natl Acad Sci U S A 94:1441–1446
Yamada Y, Webber EM, Kirillova I et al (1998) Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis factor receptor: requirement for type 1 but not type 2 receptor. Hepatology 28:959–970
Yamada Y, Fausto N (1998) Deficient liver regeneration after carbon tetrachloride injury in mice lacking type 1 but not type 2 tumor necrosis factor receptor. Am J Pathol 152: 1577–1589
Cressman DE, Greenbaum LE, DeAngelis RA et al (1996) Liver failure and defective hepatocyte regeneration in interleukin- 6-deficient mice. Science 274:1379–1383
Li W, Liang X, Kellendonk C et al (2002) STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration. J Biol Chem 277:28411–28417
Blindenbacher A, Wang X, Langer I et al (2003) Interleukin 6 is important for survival after partial hepatectomy in mice. Hepatology 38:674–682
Sakamoto T, Liu Z, Murase N et al (1999) Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy. Hepatology 29:403–411
Wuestefeld T, Klein C, Streetz KL et al (2003) Interleukin-6/glycoprotein 130-dependent pathways are protective during liver regeneration. J Biol Chem 278:11281–11288
Dierssen U, Beraza N, Lutz HH et al (2008) Molecular dissection of gp130-dependent pathways in hepatocytes during liver regeneration. J Biol Chem 283:9886–9895
Iimuro Y, Nishiura T, Hellerbrand C et al (1998) NF-κB prevents apoptosis and liver dysfunction during liver regeneration. J Clin Invest 101:802–811
DeAngelis RA, Kovalovich K, Cressman DE, Taub R (2001) Normal liver regeneration in p50/nuclear factor κB1 knockout mice. Hepatology 33:915–924
Rai RM, Lee FY, Rosen A et al (1998) Impaired liver regeneration in inducible nitric oxide synthase deficient mice. Proc Natl Acad Sci U S A 95:13829–13834
Chaisson ML, Brooling JT, Ladiges W et al (2002) Hepatocyte-specific inhibition of NF-κB leads to apoptosis after TNF treatment, but not after partial hepatectomy. J Clin Invest 110:193–202
Maeda S, Chang L, Li ZW et al (2003) IKKβ is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFα. Immunity 19:725–737
Malato Y, Sander LE, Liedtke C et al (2008) Hepatocyte-specific inhibitor-of-κB-kinase deletion triggers the innate immune response and promotes earlier cell proliferation during liver regeneration. Hepatology 47:2036–2050
Akerman PA, Cote PM, Yang SQ et al (1993) Long-term ethanol consumption alters the hepatic response to the regenerative effects of tumor necrosis factor-α. Hepatology 17:1066–1073
Yang SQ, Lin HZ, Yin M et al (1998) Effects of chronic ethanol consumption on cytokine regulation of liver regeneration. Am J Physiol 275:G696–G704
Czaja MJ, Flanders KC, Biempica L et al (1989) Expression of tumor necrosis factor-α and transforming growth factor-β 1 in acute liver injury. Growth Factors 1:219–226
McClain CJ, Hill DB, Song Z et al (2002) Monocyte activation in alcoholic liver disease. Alcohol 27:53–61
Morio LA, Chiu H, Sprowles KA et al (2001) Distinct roles of tumor necrosis factor-α and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicol Appl Pharmacol 172:44–51
Yin M, Wheeler MD, Kono H et al (1999) Essential role of tumor necrosis factor α in alcohol-induced liver injury in mice. Gastroenterology 117:942–952
Honchel R, Marsano L, Cohen D et al (1991) Lead enhances lipopolysaccharide and tumor necrosis factor liver injury. J Lab Clin Med 117:202–208
Czaja MJ, Schilsky ML, Xu Y et al (1994) Induction of MnSOD gene expression in a hepatic model of TNF-α toxicity does not result in increased protein. Am J Physiol 266:G737–G744
Xu Y, Jones BE, Neufeld DS, Czaja MJ (1998) Glutathione modulates rat and mouse hepatocyte sensitivity to tumor necrosis factor toxicity. Gastroenterology 115:1229–1237
Lou H, Kaplowitz N (2007) Glutathione depletion down-regulates tumor necrosis factor α-induced NF-κB activity via IκB kinase-dependent and -independent mechanisms. J Biol Chem 282:29470–29481
Colell A, Garcia-Ruiz C, Miranda M et al (1998) Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor. Gastroenterology 115:1541–1551
Mandrekar P, Catalano D, Jeliazkova V, Kodys K (2008) Alcohol exposure regulates heat shock transcription factor binding and heat shock proteins 70 and 90 in monocytes and macrophages: implication for TNF-α regulation. J Leukoc Biol 84:1335–1345
Haouzi D, Lekehal M, Tinel M et al (2001) Prolonged, but not acute, glutathione depletion promotes Fas-mediated mitochondrial permeability transition and apoptosis in mice. Hepatology 33:1181–1188
Koteish A, Yang S, Lin H et al (2002) Chronic ethanol exposure potentiates lipopolysaccharide liver injury despite inhibiting Jun N-terminal kinase and caspase 3 activation. J Biol Chem 277:13037–13044
Li J, Bombeck CA, Yang S et al (1999) Nitric oxide suppresses apoptosis via interrupting caspase activation and mitochondrial dysfunction in cultured hepatocytes. J Biol Chem 274:17325–17333
Arvelo MB, Cooper JT, Longo C et al (2002) A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Hepatology 35:535–543
Sass G, Shembade ND, Haimerl F et al (2007) TNF pretreatment interferes with mitochondrial apoptosis in the mouse liver by A20-mediated down-regulation of Bax. J Immunol 179:7042–7049
Tracey D, Klareskog L, Sasso EH et al (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 117:244–279
Naveau S, Chollet-Martin S, Dharancy S et al (2004) A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis. Hepatology 39:1390–1397
Spahr L, Rubbia-Brandt L, Frossard JL et al (2002) Combination of steroids with infliximab or placebo in severe alcoholic hepatitis: a randomized controlled pilot study. J Hepatol 37:448–455
Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346:1221–1231
Marchesini G, Bugianesi E, Forlani G et al (2003) Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 37:917–923
Diehl AM (2005) Lessons from animal models of NASH. Hepatol Res 33:138–144
De Taeye BM, Novitskaya T, McGuinness OP et al (2007) Macrophage TNF-α contributes to insulin resistance and hepatic steatosis in diet-induced obesity. Am J Physiol Endocrinol Metab 293:E713–E725
Dela PA, Leclercq I, Field J et al (2005) NF-κB activation, rather than TNF, mediates hepatic inflammation in a murine dietary model of steatohepatitis. Gastroenterology 129: 1663–1674
Nguyen MT, Satoh H, Favelyukis S et al (2005) JNK and tumor necrosis factor-α mediate free fatty acid-induced insulin resistance in 3T3–L1 adipocytes. J Biol Chem 280:35361–35371
Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS (1997) Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature 389:610–614
Endo M, Masaki T, Seike M, Yoshimatsu H (2007) TNF-α induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c). Exp Biol Med (Maywood) 232:614–621
Crespo J, Cayon A, Fernandez-Gil P et al (2001) Gene expression of tumor necrosis factor α and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 34:1158–1163
Hui JM, Hodge A, Farrell GC et al (2004) Beyond insulin resistance in NASH: TNF-α or adiponectin? Hepatology 40:46–54
Ruiz AG, Casafont F, Crespo J et al (2007) Lipopolysaccharide-binding protein plasma levels and liver TNF-α gene expression in obese patients: evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obes Surg 17:1374–1380
Poniachik J, Csendes A, Diaz JC et al (2006) Increased production of IL-1α and TNF-α in lipopolysaccharide-stimulated blood from obese patients with non-alcoholic fatty liver disease. Cytokine 33:252–257
Tokushige K, Takakura M, Tsuchiya-Matsushita N et al (2007) Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis. J Hepatol 46: 1104–1110
Valenti L, Fracanzani AL, Dongiovanni P et al (2002) Tumor necrosis factor α promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease. Gastroenterology 122:274–280
Tokushige K, Hashimoto E, Tsuchiya N et al (2005) Clinical significance of soluble TNF receptor in Japanese patients with non-alcoholic steatohepatitis. Alcohol Clin Exp Res 29:298S–303S
Kummee P, Tangkijvanich P, Poovorawan Y, Hirankarn N (2007) Association of HLA-DRB1*13 and TNF-α gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population. J Viral Hepat 14:841–848
Suneetha PV, Sarin SK, Goyal A et al (2006) Association between vitamin D receptor, CCR5, TNF-α and TNF-β gene polymorphisms and HBV infection and severity of liver disease. J Hepatol 44:856–863
Biermer M, Puro R, Schneider RJ (2003) Tumor necrosis factor α inhibition of hepatitis B virus replication involves disruption of capsid integrity through activation of NF-κB. J Virol 77:4033–4042
Shi H, Guan SH (2008) Increased apoptosis in HepG2.2.15 cells with hepatitis B virus expression by synergistic induction of interferon-gamma and tumour necrosis factor-α. Liver Int 29:349–355
Yared G, Hussain KB, Nathani MG et al (1998) Cytokine-mediated apoptosis and inhibition of virus production and anchorage independent growth of viral transfected hepatoblastoma cells. Cytokine 10:586–595
Kim WH, Hong F, Jaruga B et al (2005) Hepatitis B virus X protein sensitizes primary mouse hepatocytes to ethanol- and TNF-α-induced apoptosis by a caspase-3-dependent mechanism. Cell Mol Immunol 2:40–48
Wang WH, Gregori G, Hullinger RL, Andrisani OM (2004) Sustained activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase pathways by hepatitis B virus X protein mediates apoptosis via induction of Fas/FasL and tumor necrosis factor (TNF) receptor 1/TNF-α expression. Mol Cell Biol 24: 10352–10365
Kim KH, Seong BL (2003) Pro-apoptotic function of HBV X protein is mediated by interaction with c-FLIP and enhancement of death-inducing signal. EMBO J 22: 2104–2116
Su F, Theodosis CN, Schneider RJ (2001) Role of NF-κB and myc proteins in apoptosis induced by hepatitis B virus HBx protein. J Virol 75:215–225
Hassan M, Ghozlan H, Abdel-Kader O (2005) Activation of c-Jun NH2-terminal kinase (JNK) signaling pathway is essential for the stimulation of hepatitis C virus (HCV) non-structural protein 3 (NS3)-mediated cell growth. Virology 333:324–336
Hassan M, Selimovic D, Ghozlan H, Abdel-Kader O (2007) Induction of high-molecular-weight (HMW) tumor necrosis factor(TNF) α by hepatitis C virus (HCV) non-structural protein 3 (NS3) in liver cells is AP-1 and NF-κB-dependent activation. Cell Signal 19:301–311
Marusawa H, Hijikata M, Chiba T, Shimotohno K (1999) Hepatitis C virus core protein inhibits Fas- and tumor necrosis factor α-mediated apoptosis via NF-κB activation. J Virol 73:4713–4720
Zhu N, Khoshnan A, Schneider R et al (1998) Hepatitis C virus core protein binds to the cytoplasmic domain of tumor necrosis factor (TNF) receptor 1 and enhances TNF-induced apoptosis. J Virol 72:3691–3697
Acknowledgments
Supported in part by National Institutes of Health grants DK044234 and DK061498 to MJC and a Deutsche Forschungsgemeinschaft (DFG) grant to JMS.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Schattenberg, J.M., Czaja, M.J. (2010). TNF/TNF Receptors. In: Dufour, JF., Clavien, PA. (eds) Signaling Pathways in Liver Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00150-5_10
Download citation
DOI: https://doi.org/10.1007/978-3-642-00150-5_10
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-00149-9
Online ISBN: 978-3-642-00150-5
eBook Packages: MedicineMedicine (R0)