Abstract
Recent evidence indicates that cell death can be induced through multiple mechanisms. Strikingly, the same death signal can often induce apoptotic as well as non-apoptotic cell death. For instance, inhibition of caspases often converts an apoptotic stimulus to one that causes necrosis. Because a dedicated molecular circuitry distinct from that controlling apoptosis is required for necrotic cell injury, terms such as “programmed necrosis” or “necroptosis” have been used to distinguish stimulus-dependent necrosis from those induced by non-specific traumas (e.g., heat shock) or secondary necrosis induced as a consequence of apoptosis. In several experimental models, programmed necrosis/necroptosis has been shown to be a crucial control point for pathogen- or injury-induced inflammation. In this review, we will discuss the molecular mechanisms that regulate programmed necrosis/necroptosis and its biological significance in pathogen infections, drug-induced cell injury, and trauma-induced tissue damage.
Similar content being viewed by others
References
Schneider D, Gerhardt E, Bock J, Muller MM, Wolburg H, Lang F, Schulz JB (2004) Intracellular acidification by inhibition of the Na+/H+-exchanger leads to caspase-independent death of cerebellar granule neurons resembling paraptosis. Cell Death Differ 11:760–770
Jadus MR, Chen Y, Boldaji MT, Delgado C, Sanchez R, Douglass T, Al-Atar U, Schulz W, Lloyd C, Wepsic HT (2003) Human U251MG glioma cells expressing the membrane form of macrophage colony-stimulating factor (mM-CSF) are killed by human monocytes in vitro and are rejected within immunodeficient mice via paraptosis that is associated with increased expression of three different heat shock proteins. Cancer Gene Ther 10:411–420
Chen TS, Wang XP, Sun L, Wang LX, Xing D, Mok M (2008) Taxol induces caspase-independent cytoplasmic vacuolization and cell death through endoplasmic reticulum (ER) swelling in ASTC-a-1 cells. Cancer Lett 270:164–172
Fernandes-Alnemri T, Wu J, Yu JW, Datta P, Miller B, Jankowski W, Rosenberg S, Zhang J, Alnemri ES (2007) The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ 14:1590–1604
Bergsbaken T, Fink SL, Cookson BT (2009) Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7:99–109
Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y (2009) Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 10:458–467
Berry DL, Baehrecke EH (2007) Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 131:1137–1148
Samara C, Syntichaki P, Tavernarakis N (2008) Autophagy is required for necrotic cell death in Caenorhabditis elegans. Cell Death Differ 15:105–112
Koike M, Shibata M, Tadakoshi M, Gotoh K, Komatsu M, Waguri S, Kawahara N, Kuida K, Nagata S, Kominami E, Tanaka K, Uchiyama Y (2008) Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol 172:454–469
Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 1:489–495
Xu Y, Huang S, Liu ZG, Han J (2006) Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1/TRAF2-mediated JNK1 activation. J Biol Chem 281:8788–8795
Zong WX, Ditsworth D, Bauer DE, Wang ZQ, Thompson CB (2004) Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev 18:1272–1282
Declercq W, Vanden Berghe T, Vandenabeele P (2009) RIP kinases at the crossroads of cell death and survival. Cell 138:229–232
Christofferson DE, Yuan J (2010) Necroptosis as an alternative form of programmed cell death. Curr Opin Cell Biol 22:263–268
Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 146:3–15
Krysko DV, Vanden Berghe T, D’Herde K, Vandenabeele P (2008) Apoptosis and necrosis: detection, discrimination and phagocytosis. Methods 44:205–221
Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:3666–3670
Vercammen D, Beyaert R, Denecker G, Goossens V, Van Loo G, Declercq W, Grooten J, Fiers W, Vandenabeele P (1998) Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J Exp Med 187:1477–1485
Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (1996) TNF-dependent recruitment of the protein kinase RIP to the TNF receptor- 1 signaling complex. Immunity 4:387–396
Ting AT, Pimentel-Muinos FX, Seed B (1996) RIP mediates tumor necrosis factor receptor 1 activation of NF-kappaB but not Fas/APO-1-initiated apoptosis. EMBO J 15:6189–6196
Karin M, Lin A (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3:221–227
Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol 5:503–507
Cusson-Hermance N, Khurana S, Lee TH, Fitzgerald KA, Kelliher MA (2005) Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J Biol Chem 280:36560–36566
Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ, Vucic D (2008) c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J Biol Chem 283:24295–24299
Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ, Barker PA (2008) cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell 30:689–700
Mahoney DJ, Cheung HH, Mrad RL, Plenchette S, Simard C, Enwere E, Arora V, Mak TW, Lacasse EC, Waring J, Korneluk RG (2008) Both cIAP1 and cIAP2 regulate TNFalpha-mediated NF-kappaB activation. Proc Natl Acad Sci USA 105:11778–11783
Ea CK, Deng L, Xia ZP, Pineda G, Chen ZJ (2006) Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell 22:245–257
Wu CJ, Conze DB, Li T, Srinivasula SM, Ashwell JD (2006) Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]. Nat Cell Biol 8:398–406
Wong WW, Gentle IE, Nachbur U, Anderton H, Vaux DL, Silke J (2010) RIPK1 is not essential for TNFR1-induced activation of NF-kappaB. Cell Death Differ 17:482–487
Haas TL, Emmerich CH, Gerlach B, Schmukle AC, Cordier SM, Rieser E, Feltham R, Vince J, Warnken U, Wenger T, Koschny R, Komander D, Silke J, Walczak H (2009) Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol Cell 36:831–844
Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, Nakagawa T, Kato M, Murata S, Yamaoka S, Yamamoto M, Akira S, Takao T, Tanaka K, Iwai K (2009) Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol 11:123–132
Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, Appel M, Orenstein J, Moss B, Lenardo MJ (2003) A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J Biol Chem 278:51613–51621
Wang L, Du F, Wang X (2008) TNF-alpha induces two distinct caspase-8 activation pathways. Cell 133:693–703
Stanger BZ, Leder P, Lee TH, Kim E, Seed B (1995) RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 81:513–523
Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123
He S, Wang L, Miao L, Du F, Zhao L, Wang X (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-α. Cell 137:1100–1111
Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332–336
Wertz IE, O’Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430:694–699
Wright A, Reiley WW, Chang M, Jin W, Lee AJ, Zhang M, Sun SC (2007) Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD. Dev Cell 13:705–716
Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, Xavier RJ, Yuan J (2008) Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135:1311–1323
O’Donnell MA, Legarda-Addison D, Skountzos P, Yeh WC, Ting AT (2007) Ubiquitination of RIP1 regulates an NF-kappaB-independent cell-death switch in TNF signaling. Curr Biol 17:418–424
Legarda-Addison D, Hase H, O’Donnell MA, Ting AT (2009) NEMO/IKKgamma regulates an early NF-kappaB-independent cell-death checkpoint during TNF signaling. Cell Death Differ 16:1279–1288
Chan FK, Lenardo MJ (2000) A crucial role for p80 TNF-R2 in amplifying p60 TNF-R1 apoptosis signals in T lymphocytes. Eur J Immunol 30:652–660
Zheng L, Bidere N, Staudt D, Cubre A, Orenstein J, Chan FK, Lenardo M (2006) Competitive control of independent programs of tumor necrosis factor receptor-induced cell death by TRADD and RIP1. Mol Cell Biol 26:3505–3513
Lin Y, Devin A, Rodriguez Y, Liu ZG (1999) Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev 13:2514–2526
Feng S, Yang Y, Mei Y, Ma L, Zhu DE, Hoti N, Castanares M, Wu M (2007) Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain. Cell Signal 19:2056–2067
Moquin D, Chan FK (2010) The molecular regulation of programmed necrotic cell injury. Trends Biochem Sci. doi:10.1016/j.tibs.2010.03.001
Festjens N, Kalai M, Smet J, Meeus A, Van Coster R, Saelens X, Vandenabeele P (2006) Butylated hydroxyanisole is more than a reactive oxygen species scavenger. Cell Death Differ 13:166–169
Pamplona R (2008) Membrane phospholipids, lipoxidative damage and molecular integrity: a causal role in aging and longevity. Biochim Biophys Acta 1777:1249–1262
Hildeman DA, Mitchell T, Teague TK, Henson P, Day BJ, Kappler J, Marrack PC (1999) Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity 10:735–744
Sidoti-de Fraisse C, Rincheval V, Risler Y, Mignotte B, Vayssiere JL (1998) TNF-alpha activates at least two apoptotic signaling cascades. Oncogene 17:1639–1651
Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W (1992) Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem 267:5317–5323
Temkin V, Huang Q, Liu H, Osada H, Pope RM (2006) Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis. Mol Cell Biol 26:2215–2225
Kasof GM, Prosser JC, Liu D, Lorenzi MV, Gomes BC (2000) The RIP-like kinase, RIP3, induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria. FEBS Lett 473:285–291
Kim YS, Morgan MJ, Choksi S, Liu ZG (2007) TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. Mol Cell 26:675–687
Yazdanpanah B, Wiegmann K, Tchikov V, Krut O, Pongratz C, Schramm M, Kleinridders A, Wunderlich T, Kashkar H, Utermohlen O, Bruning JC, Schutze S, Kronke M (2009) Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. Nature 460:1159–1163
Rock KL, Latz E, Ontiveros F, Kono H (2010) The sterile inflammatory response. Annu Rev Immunol 28:321–342
Nagata S, Hanayama R, Kawane K (2010) Autoimmunity and the clearance of dead cells. Cell 140:619–630
Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237–241
Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, Akira S, Rock KL (2006) MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest 116:2262–2271
Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A, Abraham E (2004) Involvement of Toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 279:7370–7377
Kokkola R, Andersson A, Mullins G, Ostberg T, Treutiger CJ, Arnold B, Nawroth P, Andersson U, Harris RA, Harris HE (2005) RAGE is the major receptor for the proinflammatory activity of HMGB1 in rodent macrophages. Scand J Immunol 61:1–9
Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T (2008) Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol 9:1179–1188
Sancho D, Joffre OP, Keller AM, Rogers NC, Martinez D, Hernanz-Falcon P, Rosewell I, Reis e Sousa C (2009) Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458:899–903
Krammer PH, Arnold R, Lavrik IN (2007) Life and death in peripheral T cells. Nat Rev Immunol 7:532–542
Siegel RM (2006) Caspases at the crossroads of immune-cell life and death. Nat Rev Immunol 6:308–317
Zhang J, Cado D, Chen A, Kabra NH, Winoto A (1998) Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. Nature 392:296–300
Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, Lenardo MJ (2002) Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419:395–399
Newton K, Harris AW, Bath ML, Smith KG, Strasser A (1998) A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J 17:706–718
Walsh CM, Wen BG, Chinnaiyan AM, O’Rourke K, Dixit VM, Hedrick SM (1998) A role for FADD in T cell activation and development. Immunity 8:439–449
Salmena L, Hakem R (2005) Caspase-8 deficiency in T cells leads to a lethal lymphoinfiltrative immune disorder. J Exp Med 202:727–732
Su H, Bidere N, Zheng L, Cubre A, Sakai K, Dale J, Salmena L, Hakem R, Straus S, Lenardo M (2005) Requirement for caspase-8 in NF-kappaB activation by antigen receptor. Science 307:1465–1468
Ch’en IL, Beisner DR, Degterev A, Lynch C, Yuan J, Hoffmann A, Hedrick SM (2008) Antigen-mediated T cell expansion regulated by parallel pathways of death. Proc Natl Acad Sci USA 105:17463–17468
Bell BD, Leverrier S, Weist BM, Newton RH, Arechiga AF, Luhrs KA, Morrissette NS, Walsh CM (2008) FADD and caspase-8 control the outcome of autophagic signaling in proliferating T cells. Proc Natl Acad Sci USA 105:16677–16682
Degterev A, Hitomi J, Germscheid M, Ch’en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4:313–321
Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan J (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1:112–119
Imtiyaz HZ, Zhang Y, Zhang J (2005) Structural requirements for signal-induced target binding of FADD determined by functional reconstitution of FADD deficiency. J Biol Chem 280:31360–31367
Beisner DR, Ch’en IL, Kolla RV, Hoffmann A, Hedrick SM (2005) Cutting edge: innate immunity conferred by B cells is regulated by caspase-8. J Immunol 175:3469–3473
Benedict CA, Norris PS, Ware CF (2002) To kill or be killed: viral evasion of apoptosis. Nat Immunol 3:1013–1018
Dobo J, Swanson R, Salvesen GS, Olson ST, Gettins PG (2006) Cytokine response modifier a inhibition of initiator caspases results in covalent complex formation and dissociation of the caspase tetramer. J Biol Chem 281:38781–38790
Li M, Beg AA (2000) Induction of necrotic-like cell death by tumor necrosis factor alpha and caspase inhibitors: novel mechanism for killing virus-infected cells. J Virol 74:7470–7477
Ruby J, Bluethmann H, Peschon JJ (1997) Antiviral activity of tumor necrosis factor (TNF) is mediated via p55 and p75 TNF receptors. J Exp Med 186:1591–1596
Sambhi SK, Kohonen-Corish MR, Ramshaw IA (1991) Local production of tumor necrosis factor encoded by recombinant vaccinia virus is effective in controlling viral replication in vivo. Proc Natl Acad Sci USA 88:4025–4029
Goldmacher VS (2005) Cell death suppression by cytomegaloviruses. Apoptosis 10:251–265
Upton JW, Kaiser WJ, Mocarski ES (2010) Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe 7:302–313
Brune W, Menard C, Heesemann J, Koszinowski UH (2001) A ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism. Science 291:303–305
Mack C, Sickmann A, Lembo D, Brune W (2008) Inhibition of proinflammatory and innate immune signaling pathways by a cytomegalovirus RIP1-interacting protein. Proc Natl Acad Sci USA 105:3094–3099
Upton JW, Kaiser WJ, Mocarski ES (2008) Cytomegalovirus M45 cell death suppression requires receptor-interacting protein (RIP) homotypic interaction motif (RHIM)-dependent interaction with RIP1. J Biol Chem 283:16966–16970
Lembo D, Donalisio M, Hofer A, Cornaglia M, Brune W, Koszinowski U, Thelander L, Landolfo S (2004) The ribonucleotide reductase R1 homolog of murine cytomegalovirus is not a functional enzyme subunit but is required for pathogenesis. J Virol 78:4278–4288
Rebsamen M, Heinz LX, Meylan E, Michallet MC, Schroder K, Hofmann K, Vazquez J, Benedict CA, Tschopp J (2009) DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO Rep 10:916–922
Kaiser WJ, Upton JW, Mocarski ES (2008) Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors. J Immunol 181:6427–6434
Thome M, Schneider P, Hofmann K, Fickenscher H, Meinl E, Neipel F, Mattmann C, Burns K, Bodmer JL, Schroter M, Scaffidi C, Krammer PH, Peter ME, Tschopp J (1997) Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386:517–521
Bertin J, Armstrong RC, Ottilie S, Martin DA, Wang Y, Banks S, Wang GH, Senkevich TG, Alnemri ES, Moss B, Lenardo MJ, Tomaselli KJ, Cohen JI (1997) Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis. Proc Natl Acad Sci USA 94:1172–1176
Shisler JL, Moss B (2001) Immunology 102 at poxvirus U: avoiding apoptosis. Semin Immunol 13:67–72
Yang JK, Wang L, Zheng L, Wan F, Ahmed M, Lenardo MJ, Wu H (2005) Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition. Mol Cell 20:939–949
Garvey TL, Bertin J, Siegel RM, Wang GH, Lenardo MJ, Cohen JI (2002) Binding of FADD and caspase-8 to molluscum contagiosum virus MC159 v-FLIP is not sufficient for its antiapoptotic function. J Virol 76:697–706
Thurau M, Everett H, Tapernoux M, Tschopp J, Thome M (2006) The TRAF3-binding site of human molluscipoxvirus FLIP molecule MC159 is critical for its capacity to inhibit Fas-induced apoptosis. Cell Death Differ 13:1577–1585
Chaudhary PM, Jasmin A, Eby MT, Hood L (1999) Modulation of the NF-kappa B pathway by virally encoded death effector domains-containing proteins. Oncogene 18:5738–5746
Woelfel M, Bixby J, Brehm MA, Chan FK (2006) Transgenic expression of the viral FLIP MC159 causes lpr/gld-like lymphoproliferation and autoimmunity. J Immunol 177:3814–3820
Murao LE, Shisler JL (2005) The MCV MC159 protein inhibits late, but not early, events of TNF-alpha-induced NF-kappaB activation. Virology 340:255–264
Kennedy CL, Smith DJ, Lyras D, Chakravorty A, Rood JI (2009) Programmed cellular necrosis mediated by the pore-forming alpha-toxin from Clostridium septicum. PLoS Pathog 5:e1000516
Grobner S, Autenrieth SE, Soldanova I, Gunst DS, Schaller M, Bohn E, Muller S, Leverkus M, Wesselborg S, Autenrieth IB, Borgmann S (2006) Yersinia YopP-induced apoptotic cell death in murine dendritic cells is partially independent from action of caspases and exhibits necrosis-like features. Apoptosis 11:1959–1968
Kirschnek S, Scheffel J, Heinzmann U, Hacker G (2004) Necrosis-like cell death induced by bacteria in mouse macrophages. Eur J Immunol 34:1461–1471
Mareninova OA, Sung KF, Hong P, Lugea A, Pandol SJ, Gukovsky I, Gukovskaya AS (2006) Cell death in pancreatitis: caspases protect from necrotizing pancreatitis. J Biol Chem 281:3370–3381
Malleo G, Mazzon E, Genovese T, Di Paola R, Muia C, Centorrino T, Siriwardena AK, Cuzzocrea S (2007) Etanercept attenuates the development of cerulein-induced acute pancreatitis in mice: a comparison with TNF-alpha genetic deletion. Shock 27:542–551
Sandoval J, Pereda J, Rodriguez JL, Escobar J, Hidalgo J, Joosten LA, Franco L, Sastre J, Lopez-Rodas G (2010) Ordered transcriptional factor recruitment and epigenetic regulation of TNF-alpha in necrotizing acute pancreatitis. Cell Mol Life Sci 67:1687–1697
Zhang M, Chen L (2008) Status of cytokines in ischemia reperfusion induced heart injury. Cardiovasc Hematol Disord Drug Targets 8:161–172
Stoll G, Jander S, Schroeter M (2002) Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system. Adv Exp Med Biol 513:87–113
You Z, Savitz SI, Yang J, Degterev A, Yuan J, Cuny GD, Moskowitz MA, Whalen MJ (2008) Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice. J Cereb Blood Flow Metab 28:1564–1573
Smith CC, Davidson SM, Lim SY, Simpkin JC, Hothersall JS, Yellon DM (2007) Necrostatin: a potentially novel cardioprotective agent? Cardiovasc Drugs Ther 21:227–233
Acknowledgments
This work is supported by NIH grants AI088502 and AI083497 (to F.K.C.). F.K.C. is a member of the UMass DERC (DK32520). We thank J. Upton, W. Kaiser and E. Mocarski for sharing their results ahead of print publication.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Challa, S., Chan, F.KM. Going up in flames: necrotic cell injury and inflammatory diseases. Cell. Mol. Life Sci. 67, 3241–3253 (2010). https://doi.org/10.1007/s00018-010-0413-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00018-010-0413-8