Defending the liver from inflammation Christian Trautwein Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. * To whom correspondence should be sent: Professor Dr. med. C. Trautwein, Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg- Strasse 1, 30625 Hannover Tel.: +49-511-532-6620, Fax: +49-511-532-5692 Email: [email protected]
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Defending the liver from inflammation
Christian Trautwein
Department of Gastroenterology, Hepatology and Endocrinology, Medizinische
became activated and phosphorylate tyrosines as the intracellular part of gp130. The
phosphorylated tyrosines are essential to activate downstream pathways. While
phosphorylation of the second tyrosine is important to trigger the Ras/Map pathway
via SH2-domain containing protein tyrosine phosphatase 2 (Shp2), the four distal
tyrosines are essential to activate Stat transcription factors.
Figure 2. TNF-dependent signal transduction
Engagement of TNF with its cognate receptor TNF-R1 results in the release of SODD
and formation of a receptor-proximal complex containing the important adapter
proteins TRADD, TRAF2, RIP, and FADD. These adapter proteins in turn recruit
additional key pathway-specific enzymes (for example, caspase-8 and IKK2) to the
TNF-R1 complex, where they become activated and initiate downstream events
leading to apoptosis via caspase 8, NF- B activation involving the IKK-complex, and
Junkinase (JNK) activation.
Literature:
Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science 1998, 281: 1305-7.
Bajt ML, Lawson JA, Vonderfecht SL, Gujral JS, Jaeschke H. Protection against Fas receptor-mediated apoptosis in hepatocytes and nonparenchymal cells by a caspase-8 inhibitor in vivo: evidence for a postmitochondrial processing of caspase-8. Toxicol Sci. 2000; 58: 109-18.
Behrens A, Sibilia M, David JP, Mohle-Steinlein U, Tronche F, Schutz G, Wagner EF. Impaired postnatal hepatocyte proliferation and liver regeneration in mice lacking c-jun in the liver. EMBO J. 2002; 21: 1782-90.
Betz UA, Bloch W, van den Broek M, Yoshida K, Taga T, Kishimoto T, Addicks K, Rajewsky K, Muller W. Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects. J Exp Med. 1998; 188: 1955-65.
Bird GLA, Sheron N, Goka J, Alexander GJ, Williams RS. Increased plasma tumor necrosis factor in severe alcoholic hepatitis. Ann Intern Med. 1990: 112: 917-24.
Blindenbacher A, Wang X, Langer I, Savino R, Terracciano L, Heim MH. Interleukin 6 is important for survival after partial hepatectomy in mice. Hepatology. 2003; 38: 674-82.
Campbell JS, Prichard L, Schaper F, Schmitz J, Stephenson-Famy A, Rosenfeld ME, Argast GM, Heinrich PC, Fausto N. Expression of suppressors of cytokine signaling during liver regeneration. J Clin Invest. 2001; 107: 1285-92
Chaisson ML, Brooling JT, Ladiges W, Tsai S, Fausto N. Hepatocyte-specific inhibition of NF-kappaB leads to apoptosis after TNF treatment, but not after partial hepatectomy. J Clin Invest. 2002; 110: 193-202
Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA. 1975; 72: 3666-72.
Catlett-Falcone R, Landowski TH, Oshiri MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinksi L, Fernandez-Luna JL, Nunez G, Dalton WS, Jove R. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 1999; 10: 105-13.
Chen RH, Chang MC, Su YH, Tsai YT, Kuo ML. Interleukin-6 inhibits transforming growth factor-beta-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways. J Biol Chem. 1999; 274: 23013-21.
Chen, G. and D. V. Goeddel. TNF-R1 signaling: a beautiful pathway. Science 2002; 296: 1634-1635
Colletti LM, Remick DG, Burtch GD, Kunkel SL, Strieter RM, Campbell DA. Role of tumor necrosis factor- in the pathophysiological alterations after ischemia/reperfusion injury in the rat. J Clin Invest. 1990; 85: 1936-43.
Cressman, D. E., L. E. Greenbaum, B. A. Haber, and R. Taub. Rapid activation of post-hepatectomy factor/nuclear factor kappa B in hepatocytes, a primary response in the regenerating liver. J. Biol. Chem. 1994; 269: 30429-30435.
Cressman DE, Diamond RH, Taub R. Rapid activation of the Stat3 transcription complex in liver regeneration. Hepatology. 1995; 21: 1443-9.
Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poli V, Taub R. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science. 1996; 274: 1379-83.
Delhase, M., M. Hayakawa, Y. Chen, and M. Karin. Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science 1999; 284: 309-313.
DiDonato, J. A., M. Hayakawa, D. M. Rothwarf, E. Zandi, and M. Karin. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 1997; 388: 548-554.
Diehl AM, Yin M, Fleckenstein J, Yang SQ, Lin HZ, Brenner DA, Westwick J, Bagby G, Nelson S.Tumor necrosis factor-alpha induces c-jun during the regenerative response to liver injury. Am J Physiol. 1994; 267: G552-61.
Feinberg B, Kurzrock R, Talpaz M, Blick M, Saks S, Gutterman JU. A phase I trial of intravenously-administered recombinant human tumor necrosis factor-alpha in cancer patients. J Clin Oncol. 1988; 6: 1328-35.
Felver ME, Mezey E, McGuire M, Mitchel MC, Herlong F, Veech GA and Veech RL. Plasma tumor necrosis factor- predicts decreased long-term survival in severe alcoholic hepatitis. Alcohol Clin Exp Res. 1990; 14: 255-62.
Galle PR, Hofmann WJ, Walczak H, Schaller H, Otto G, Stremmel W, Krammer PH, Runkel L. Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med. 1995; 182: 1223-30.
Galle P, Krammer P. CD95-induced apoptosis in human liver disease. Semin Liver Dis. 1998; 18: 141-9.
Gantner F, Leist M, Lohse AW, Germann PG, Tiegs G. Concavalin A-induced T-cell-mediated hepatic injury in mice: the role of tumor necrosis factor. Hepatology. 1995; 21: 190-9.
Gonzales-Amaro R, Garcia-Monzon C, Garcia-Buey L, Moreno-Otero R, Alonso JL, Yague E, Pivel JP, Lopez-Cabrera M, Fernandez-Ruiz E, Sanchez-Madrid F. Induction of tumor necrosis factor alpha by human hepatocytes in chronic viral hepatitis. J Exp Med. 1994; 179: 841-9.
Guttridge, D. C., C. Albanese, J. Y. Reuther, R. G. Pestell, and A. S. Baldwin, Jr. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell Biol. 1999; 19: 5785-5799.
Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 1998; 334: 297-314.
Hinz, M., D. Krappmann, A. Eichten, A. Heder, C. Scheidereit, and M. Strauss. NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. Mol. Cell Biol. 1999; 19: 2690-2698.
Kaneko Y, Harada M, Kawano T, Yamashita M, Shibata Y, Gejyo F, Nakayama T, Taniguchi M. Augmentation of Valpha14 NKT cell-mediated cytotoxicity by interleukin 4 in an autocrine mechanism resulting in the development of concanavalin A-induced hepatitis. J Exp Med. 2000; 191: 105-14.
Karin, M. How NF-kappaB is activated: the role of the IkappaB kinase (IKK) complex. Oncogene 1999; 18: 6867-6874.
Kimura K, Taguchi T, Urushizaki I, Ohno R, Abe O, Furure H, Hattori T, Ichihashi H, Inoguchi K, Majima H. Phase I study of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol. 1987; 20: 223-8.
Klein C, Wuestefeld T, Aßmus U, Ernst M, Roskams T, Rose-John S, Müller M, Manns M, Trautwein C The Interleukin-6/gp130/STAT3 pathway in hepatocytes triggers liver protection in T-cell mediated liver injury J. Clin Invest, 2005 in press
Kovalovich, K., Li, W., DeAngelis, R., Greenbaum, L.E., Ciliberto, G., and Taub, R. Interleukin-6 protects against Fas-mediated death by establishing a critical level of anti-apoptotic hepatic proteins FLIP, Bcl-2, and Bcl-xL. J. Biol. Chem. 2001; 276: 26605-13.
Krammer P. CD95 (APO-1/Fas)-mediated apoptosis: live and let die. Adv Immunol. 1999; 71: 163-72.
Küsters S, Gantner F, Kunstle G, Tiegs G. Interferon gamma plays a critical role in T cell-dependent liver injury in mice initiated by concanavalin A. Gastroenterology. 1996; 111: 462-71.
Leist M, Gantner F, Naumann H, Bluethmann H, Vogt K, Brigelius-Flohe R, Nicotera P, Volk HD. Tumor necrosis factor-induced apoptosis during poisoning of mice with hepatotoxins. Gastroenterology 1997; 112: 923-9.
Li W, Liang X, Kellendonk C, Poli V, Taub R. STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration. J Biol. Chem. 2002; 277: 28411-7.
Limuro Y, Nishiura T, Hellerbrand C, Behrns KE, Schoonhoven R, Grisham JW, Brenner DA. NFkappaB prevents apoptosis and liver dysfunction during liver regeneration. J Clin Invest. 1998; 101: 802-11.
Li H, Zhu H, Xu CJ, Yuan J. 1998. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 1998; 94: 491-501.
Ludwig H, Nachbaur DM, Fritz E, Krainer M, Huber H. Interleukin-6 is a prognostic factor in multiple myeloma. Blood 1991; 77: 2794-802.
Luo X, Budihardjo I, Zou H, Slaughter C, Wang X. Bid, a Bcl-2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 1998; 94: 481-492.
Mizuhara, H., O´Neill, E., Seki, N., Ogawa, T., Kusunoki, C., Otsuka, K., Satoh, S., Niwa, M., Senoh, H. and Fujiwara, H. T-cell activation-associated hepatic-injury: Mediation by tumor necrosis factor and protection by interleukin 6. J. Exp. Med. 1994; 179: 1529-37.
Muto Y, Nouri-Aria KT, Meager A, Alexander GJ, Eddleston AL, Williams R. Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. Lancet 1988; 8602: 72-81.
Ogasawara J, Watanabe-Fukunaga R, Adachi M, Matsuzuwa A, Kasugai T, Kitamura, Y, Itoh N, Suda T, Nagata S. Lethal effect of the anti-Fas antibody in mice. Nature 1993; 364: 806-9.
Pfeffer K, Matsuyama T, Kundig M, Wakeha A, Kishiara K, Shahinian A, Wiegmann PS, Ohashi M, Kronke M, Mak TW. Mice deficient for the 55 kD tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L.monocytogenes infection. Cell. 1993; 73: 457-466.
Regnier, C. H., H. Y. Song, X. Gao, D. V. Goeddel, Z. Cao, M. Rothe. Identification and characterization of an IkappaB kinase. Cell 1997; 90: 373-383.
Ren X, Hogaboam C, Carpenter A, Colletti L. Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy. J Clin Invest. 2003; 112: 1407-18.
Rothwarf, D. M., E. Zandi, G. Natoli, M. Karin. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature 1998; 395: 297-300.
Schwabe RF, Bradham CA, Uehara T, Hatano E, Bennett BL, Schoonhoven R, Brenner DA. c-Jun-N-terminal kinase drives cyclin D1 expression and proliferation during liver regeneration. Hepatology. 2003; 37: 824-32.
Streetz K, Leifeld L, Grundmann D, Ramakers J, Eckert K, Spengler U, Brenner D, Manns M, Trautwein C. Tumor Necrosis Factor in the Pathogenesis of Human and Murine Fulminant Hepatic Failure. Gastroenterology 2000; 119: 446-455.
Streetz KL, Wustefeld T, Klein C, Kallen KJ, Tronche F, Betz UA, Schutz G, Manns MP, Muller W, Trautwein C. Lack of gp130 expression in hepatocytes promotes liver injury. Gastroenterology. 2003; 125: 532-43.
Strey CW, Markiewski M, Mastellos D, Tudoran R, Spruce LA, Greenbaum LE, Lambris JD. The proinflammatory mediators C3a and C5a are essential for liver regeneration. J Exp Med. 2003; 198: 913-23.
Taga T., Kishimoto T. Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 1997;15:797-819.
Takeda K, Noguchi K, Shi W, Tanaka T, Matsumoto M, Yoshida N, Kishimoto T, Akira S. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci U S A. 1997; 94: 3801-4.
Takeda K, Hayakawa Y, Van Kaer L, Matsuda H, Yagita H, Okumura K. Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc Natl Acad Sci U S A. 2000; 97: 5498-503.
Tiegs G, Hentschel J, Wendel A. A T cell-dependent experimental liver injury in mice inducible by concanavalin A. J Clin Invest. 1992; 90: 196-203.
Trauth B, Klas C, Peters A, Matzku S, Moller P, Falk W, Debatin K, Krammer P. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 1989; 245: 301-4.
Trautwein C, Rakemann T, Niehof M, Rose-John S, Manns MP. Acute-phase response factor, increased binding, and target gene transcription during liver regeneration. Gastroenterology. 1996; 110: 1854-62.
Tsutamoto T, Hisanaga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabuchi N, Sawaki M, Kinoshita M. Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol. 1998; 31: 391-9.
Westwick JK, Weitzel C, Leffert HL, Brenner DA.Activation of Jun kinase is an early event in hepatic regeneration. J Clin Invest. 1995; 95: 803-10.
Woronicz, J. D., X. Gao, Z. Cao, M. Rothe, D. V. Goeddel. IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science 1997; 278: 866-869.
Yamada, Y., I. Kirillova, J. J. Peschon, N. Fausto. 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 1997; 94: 1441-1446.
Yamaoka S, Courtois G, Bessia C, Whiteside ST, Weil R, Agou F, Kirk HE, Kay RJ, Israel A. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation. Cell. 1998; 93: 1231-40.
Yamamoto, Y, R. B. Gaynor. IkappaB kinases: key regulators of the NF-kappaB pathway. Trends Biochem. Sci. 2004; 29: 72-79.
Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell. 1997; 91: 243-52
Zandi, E., Y. Chen, M. Karin. Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate. Science 1998; 281: 1360-1363.
Zoratti M, Szabo I. 1995. The mitochondrial permeability transition. Biochim Biophys Acta 1995; 1241: 139-46.