NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma
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Fattovich, G., Stroffolini, T., Zagni, I. & Donato, F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127 (Suppl. 1), S35–S50 (2004).
Bonacchi, A. et al. The chemokine CCL21 modulates lymphocyte recruitment and fibrosis in chronic hepatitis C. Gastroenterology 125, 1060–1076 (2003).
Guo, J. et al. Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of Toll-like receptor 4 to hepatic stellate cell responses. Hepatology 49, 960–968 (2009).
Seki, E. et al. CCR1 and CCR5 promote hepatic fibrosis in mice. J. Clin. Invest. 119, 1858–1870 (2009).
Dominguez, M. et al. Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis. Gastroenterology 136, 1639–1650 (2009).
Miura, K. et al. Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1β in mice. Gastroenterology 139, 323–334.e7 (2010).
Karin, M. & Ben-Neriah, Y. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu. Rev. Immunol. 18, 621–663 (2000).
Xiao, C. & Ghosh, S. NF-κB, an evolutionarily conserved mediator of immune and inflammatory responses. Adv. Exp. Med. Biol. 560, 41–45 (2005).
Reddy, J. K. & Rao, M. S. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G852–G858 (2006).
Mandrekar, P. & Szabo, G. Signalling pathways in alcohol-induced liver inflammation. J. Hepatol. 50, 1258–1266 (2009).
Videla, L. A. et al. Liver NF-κB and AP-1 DNA binding in obese patients. Obesity (Silver Spring) 17, 973–979 (2009).
Hösel, M. et al. Not interferon, but interleukin-6 controls early gene expression in hepatitis B virus infection. Hepatology 50, 1773–1782 (2009).
Boya, P. et al. Nuclear factor-κB in the liver of patients with chronic hepatitis C: decreased RelA expression is associated with enhanced fibrosis progression. Hepatology 34, 1041–1048 (2001).
Tai, D. I. et al. Activation of nuclear factor κB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis. Hepatology 31, 656–664 (2000).
Kosters, A. & Karpen, S. J. The role of inflammation in cholestasis: clinical and basic aspects. Semin. Liver Dis. 30, 186–194 (2010).
Luedde, T. et al. Deletion of NEMO/IKKγ in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma. Cancer Cell 11, 119–132 (2007).
Luedde, T. et al. IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver. Proc. Natl Acad. Sci. USA 105, 9733–9738 (2008).
Bettermann, K. et al. TAK1 suppresses a NEMO-dependent but NF-κB-independent pathway to liver cancer. Cancer Cell 17, 481–496 (2010).
Inokuchi, S. et al. Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis. Proc. Natl Acad. Sci. USA 107, 844–849 (2010).
Schmitz, M. L., Mattioli, I., Buss, H. & Kracht, M. NF-κB: a multifaceted transcription factor regulated at several levels. Chembiochem 5, 1348–1358 (2004).
Schmitz, M. L. & Baeuerle, P. A. The p65 subunit is responsible for the strong transcription activating potential of NF-κB. EMBO J. 10, 3805–3817 (1991).
Amir, R. E., Haecker, H., Karin, M. & Ciechanover, A. Mechanism of processing of the NF-κB2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCF(β-TrCP) ubiquitin ligase. Oncogene 23, 2540–2547 (2004).
Saha, A., Hammond, C. E., Trojanowska, M. & Smolka, A. J. Helicobacter pylori-induced H, K-ATPase α-subunit gene repression is mediated by NF-κB p50 homodimer promoter binding. Am. J. Physiol. Gastrointest. Liver Physiol. 294, G795–G807 (2008).
West, A. P., Koblansky, A. A. & Ghosh, S. Recognition and signaling by toll-like receptors. Annu. Rev. Cell Dev. Biol. 22, 409–437 (2006).
Pahl, H. L. Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18, 6853–6866 (1999).
Hoffmann, A., Natoli, G. & Ghosh, G. Transcriptional regulation via the NF-κB signaling module. Oncogene 25, 6706–6716 (2006).
Senftleben, U. et al. Activation by IKKα of a second, evolutionary conserved, NF-κB signaling pathway. Science 293, 1495–1499 (2001).
Dejardin, E. The alternative NF-κB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem. Pharmacol. 72, 1161–1179 (2006).
Yaron, A. et al. Identification of the receptor component of the IκBα-ubiquitin ligase. Nature 396, 590–594 (1998).
Rao, P. et al. IκBβ acts to inhibit and activate gene expression during the inflammatory response. Nature 466, 1115–1119 (2010).
Delhase, M., Hayakawa, M., Chen, Y. & Karin, M. Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation. Science 284, 309–313 (1999).
Mercurio, F. et al. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science 278, 860–866 (1997).
Woronicz, J. D., Gao, X., Cao, Z., Rothe, M. & Goeddel, D. V. IκB kinase-β: NF-κB activation and complex formation with IκB kinase-α and NIK. Science 278, 866–869 (1997).
Zandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M. & Karin, M. The IκB kinase complex (IKK) contains two kinase subunits, IKKα and IKKβ, necessary for IκB phosphorylation and NF-κB activation. Cell 91, 243–252 (1997).
Anest, V. et al. A nucleosomal function for IκB kinase-α in NF-κB-dependent gene expression. Nature 423, 659–663 (2003).
Gareus, R. et al. Normal epidermal differentiation but impaired skin-barrier formation upon keratinocyte-restricted IKK1 ablation. Nat. Cell Biol. 9, 461–469 (2007).
Hu, M. C. et al. IκB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell 117, 225–237 (2004).
Zhao, T. et al. The NEMO adaptor bridges the nuclear factor-κB and interferon regulatory factor signaling pathways. Nat. Immunol. 8, 592–600 (2007).
Dong, J., Jimi, E., Zhong, H., Hayden, M. S. & Ghosh, S. Repression of gene expression by unphosphorylated NF-κB p65 through epigenetic mechanisms. Genes Dev. 22, 1159–1173 (2008).
Dong, J., Jimi, E., Zeiss, C., Hayden, M. S. & Ghosh, S. Constitutively active NF-κB triggers systemic TNFα-dependent inflammation and localized TNFα-independent inflammatory disease. Genes Dev. 24, 1709–1717 (2010).
Arenzana-Seisdedos, F. et al. Nuclear localization of IκBα promotes active transport of NF-κB from the nucleus to the cytoplasm. J. Cell Sci. 110, 369–378 (1997).
O'Connell, R. M., Taganov, K. D., Boldin, M. P., Cheng, G. & Baltimore, D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc. Natl Acad. Sci. USA 104, 1604–1609 (2007).
Karin, M. NF-κB as a critical link between inflammation and cancer. Cold Spring Harb. Perspect. Biol. 1, a000141 (2009).
Mencin, A., Kluwe, J. & Schwabe, R. F. Toll-like receptors as targets in chronic liver diseases. Gut 58, 704–720 (2009).
Wasmuth, H. E., Tacke, F. & Trautwein, C. Chemokines in liver inflammation and fibrosis. Semin. Liver Dis. 30, 215–225 (2010).
Schwabe, R. F., Seki, E. & Brenner, D. A. Toll-like receptor signaling in the liver. Gastroenterology 130, 1886–1900 (2006).
Luedde, T. & Trautwein, C. Intracellular survival pathways in the liver. Liver Int. 26, 1163–1174 (2006).
Beutler, B. & Grau, G. E. Tumor necrosis factor in the pathogenesis of infectious diseases. Crit. Care Med. 21 (10 Suppl.), S423–S435 (1993).
FitzGerald, M. J., Webber, E. M., Donovan, J. R. & Fausto, N. Rapid DNA binding by nuclear factor κB in hepatocytes at the start of liver regeneration. Cell Growth Differ. 6, 417–427 (1995).
Leist, M. et al. Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-α requires transcriptional arrest. J. Immunol. 153, 1778–1788 (1994).
Lehmann, V., Freudenberg, M. A. & Galanos, C. Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J. Exp. Med. 165, 657–663 (1987).
Leist, M. et al. Tumor necrosis factor-induced apoptosis during the poisoning of mice with hepatotoxins. Gastroenterology 112, 923–934 (1997).
Beg, A. A. & Baltimore, D. An essential role for NF-κB in preventing TNF-α-induced cell death. Science 274, 782–784 (1996).
Doi, T. S. et al. Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality. Proc. Natl Acad. Sci. USA 96, 2994–2999 (1999).
Iimuro, Y. et al. NFkappaB prevents apoptosis and liver dysfunction during liver regeneration. J. Clin. Invest. 101, 802–811 (1998).
Xu, Y. et al. NF-κB inactivation converts a hepatocyte cell line TNF-α response from proliferation to apoptosis. Am. J. Physiol. 275, C1058–C1066 (1998).
Grossmann, M. et al. The combined absence of the transcription factors Rel and RelA leads to multiple hemopoietic cell defects. Proc. Natl Acad. Sci. USA 96, 11848–11853 (1999).
Li, Q., Van Antwerp, D., Mercurio, F., Lee, K. F. & Verma, I. M. Severe liver degeneration in mice lacking the IκB kinase 2 gene. Science 284, 321–325 (1999).
Li, Z. W. et al. The IKKβ subunit of IκB kinase (IKK) is essential for nuclear factor κB activation and prevention of apoptosis. J. Exp. Med. 189, 1839–1845 (1999).
Tanaka, M. et al. Embryonic lethality, liver degeneration, and impaired NF-κB activation in IKK-β-deficient mice. Immunity 10, 421–429 (1999).
Rudolph, D. et al. Severe liver degeneration and lack of NF-κB activation in NEMO/IKKγ-deficient mice. Genes Dev. 14, 854–862 (2000).
Hu, Y. et al. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKα subunit of IκB kinase. Science 284, 316–320 (1999).
Maeda, S. et al. IKKβ is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFα. Immunity 19, 725–737 (2003).
Luedde, T. et al. 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 (2005).
De Smaele, E. et al. Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling. Nature 414, 308–313 (2001).
Tang, G. et al. Inhibition of JNK activation through NF-κB target genes. Nature 414, 313–317 (2001).
Schwabe, R. F. et al. Differential requirement for c-Jun NH2-terminal kinase in TNFα- and Fas-mediated apoptosis in hepatocytes. FASEB J. 18, 720–722 (2004).
Chen, F., Castranova, V., Li, Z., Karin, M. & Shi, X. Inhibitor of nuclear factor κB kinase deficiency enhances oxidative stress and prolongs c-Jun NH2-terminal kinase activation induced by arsenic. Cancer Res. 63, 7689–7693 (2003).
Kamata, H. et al. Reactive oxygen species promote TNFα-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120, 649–661 (2005).
Chang, L. et al. The E3 ubiquitin ligase itch couples JNK activation to TNFα-induced cell death by inducing c-FLIP(L) turnover. Cell 124, 601–613 (2006).
Das, M. et al. Induction of hepatitis by JNK-mediated expression of TNF-α. Cell 136, 249–260 (2009).
Heinrichsdorff, J., Luedde, T., Perdiguero, E., Nebreda, A. R. & Pasparakis, M. p38α MAPK inhibits JNK activation and collaborates with IκB kinase 2 to prevent endotoxin-induced liver failure. EMBO Rep. 9, 1048–1054 (2008).
Bromberg, J. & Wang, T. C. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 15, 79–80 (2009).
Naugler, W. E. & Karin, M. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol. Med. 14, 109–119 (2008).
Iliopoulos, D., Jaeger, S. A., Hirsch, H. A., Bulyk, M. L. & Struhl, K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol. Cell 39, 493–506 (2010).
Hammel, P. et al. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N. Engl. J. Med. 344, 418–423 (2001).
Muretto, P., Angelucci, E. & Lucarelli, G. Reversibility of cirrhosis in patients cured of thalassemia by bone marrow transplantation. Ann. Intern. Med. 136, 667–672 (2002).
Shiratori, Y. et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann. Intern. Med. 132, 517–524 (2000).
Friedman, S. L. Mechanisms of disease: Mechanisms of hepatic fibrosis and therapeutic implications. Nat. Clin. Pract. Gastroenterol. Hepatol. 1, 98–105 (2004).
Duffield, J. S. et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest. 115, 56–65 (2005).
Son, G. et al. Selective inactivation of NF-κB in the liver using NF-κB decoy suppresses CCl4-induced liver injury and fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 293, G631–G639 (2007).
Paik, Y. H. et al. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology 37, 1043–1055 (2003).
Hellerbrand, C. et al. Inhibition of NFκB in activated rat hepatic stellate cells by proteasome inhibitors and an IκB super-repressor. Hepatology 27, 1285–1295 (1998).
Oakley, F. et al. Angiotensin II activates IκB kinase phosphorylation of RelA at Ser 536 to promote myofibroblast survival and liver fibrosis. Gastroenterology 136, 2334–2344.e1 (2009).
Schwabe, R. F., Schnabl, B., Kweon, Y. O. & Brenner, D. A. CD40 activates NF-κB and c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells. J. Immunol. 166, 6812–6819 (2001).
Elsharkawy, A. M. et al. Persistent activation of nuclear factor-κB in cultured rat hepatic stellate cells involves the induction of potentially novel Rel-like factors and prolonged changes in the expression of IκB family proteins. Hepatology 30, 761–769 (1999).
Kluwe, J. et al. Modulation of hepatic fibrosis by c-Jun-N-terminal kinase inhibition. Gastroenterology 138, 347–359 (2010).
De Minicis, S. et al. Gene expression profiles during hepatic stellate cell activation in culture and in vivo . Gastroenterology 132, 1937–1946 (2007).
Rippe, R. A., Schrum, L. W., Stefanovic, B., Solis-Herruzo, J. A. & Brenner, D. A. NF-κB inhibits expression of the α1(I) collagen gene. DNA Cell Biol. 18, 751–761 (1999).
Gieling, R. G. et al. The c-Rel subunit of nuclear factor-κB regulates murine liver inflammation, wound-healing, and hepatocyte proliferation. Hepatology 51, 922–931 (2010).
Elsharkawy, A. M. et al. The NF-κB p50:p50:HDAC-1 repressor complex orchestrates transcriptional inhibition of multiple pro-inflammatory genes. J. Hepatol. 53, 519–527 (2010).
Oakley, F. et al. Nuclear factor-κB1 (p50) limits the inflammatory and fibrogenic responses to chronic injury. Am. J. Pathol. 166, 695–708 (2005).
Gäbele, E. et al. Role of TLR9 in hepatic stellate cells and experimental liver fibrosis. Biochem. Biophys. Res. Commun. 376, 271–276 (2008).
Watanabe, A. et al. Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9. Hepatology 46, 1509–1518 (2007).
Rutenburg, A. M. et al. The role of intestinal bacteria in the development of dietary cirrhosis in rats. J. Exp. Med. 106, 1–14 (1957).
Broitman, S. A., Gottlieb, L. S. & Zamcheck, N. Influence of neomycin and ingested endotoxin in the pathogenesis of choline deficiency cirrhosis in the adult rat. J. Exp. Med. 119, 633–642 (1964).
Iredale, J. P. et al. Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J. Clin. Invest. 102, 538–549 (1998).
Oakley, F. et al. Inhibition of inhibitor of κB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology 128, 108–120 (2005).
Roderburg, C. et al. Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology doi:10.1002/hep.23922.
Liu, P. et al. Activation of NF-κB, AP-1 and STAT transcription factors is a frequent and early event in human hepatocellular carcinomas. J. Hepatol. 37, 63–71 (2002).
Kim, H. R., Lee, S. H. & Jung, G. The hepatitis B viral X protein activates NF-κB signaling pathway through the up-regulation of TBK1. FEBS Lett. 584, 525–530 (2010).
Zhang, F., Wang, Q., Ye, L., Feng, Y. & Zhang, X. Hepatitis B virus X protein upregulates expression of calpain small subunit 1 via nuclear factor-κB/p65 in hepatoma cells. J. Med. Virol. 82, 920–928 (2010).
Lu, B. et al. Increased expression of iASPP, regulated by hepatitis B virus X protein-mediated NF-κB activation, in hepatocellular carcinoma. Gastroenterology 139, 2183–2194 (2010).
Shi, H. et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116, 3015–3025 (2006).
Pikarsky, E. et al. NF-κB functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461–466 (2004).
Haybaeck, J. et al. A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell 16, 295–308 (2009).
Maeda, S., Kamata, H., Luo, J. L., Leffert, H. & Karin, M. IKKβ couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121, 977–990 (2005).
Sakurai, T., Maeda, S., Chang, L. & Karin, M. Loss of hepatic NF-κB activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc. Natl Acad. Sci. USA 103, 10544–10551 (2006).
He, G. et al. Hepatocyte IKKβ/NF-κB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell 17, 286–297 (2010).
Calle, E. E., Rodriguez, C., Walker-Thurmond, K. & Thun, M. J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 348, 1625–1638 (2003).
Nordenstedt, H., White, D. L. & El-Serag, H. B. The changing pattern of epidemiology in hepatocellular carcinoma. Dig. Liver Dis. 42 (Suppl. 3), S206–S214 (2010).
El-Serag, H. B., Tran, T. & Everhart, J. E. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 126, 460–468 (2004).
Jee, S. H. et al. Fasting serum glucose level and cancer risk in Korean men and women. JAMA 293, 194–202 (2005).
Ribeiro, P. S. et al. Hepatocyte apoptosis, expression of death receptors, and activation of NF-κB in the liver of nonalcoholic and alcoholic steatohepatitis patients. Am. J. Gastroenterol. 99, 1708–1717 (2004).
Arkan, M. C. et al. IKK-β links inflammation to obesity-induced insulin resistance. Nat. Med. 11, 191–198 (2005).
Cai, D. et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat. Med. 11, 183–190 (2005).
Wunderlich, F. T. et al. Hepatic NF-κB essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis. Proc. Natl Acad. Sci. USA 105, 1297–1302 (2008).
Park, E. J. et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140, 197–208 (2010).
Hou, Y., Li, F., Karin, M. & Ostrowski, M. C. Analysis of the IKKβ/NF-κB signaling pathway during embryonic angiogenesis. Dev. Dyn. 237, 2926–2935 (2008).
Llovet, J. M. et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378–390 (2008).
Wang, Y. et al. New insights into the antifibrotic effects of sorafenib on hepatic stellate cells and liver fibrosis. J. Hepatol. 53, 132–144 (2010).