ME3738 protects from concanavalin A-induced liver failure via an IL-6-dependent mechanism

European Journal of Immunology

Volumn 33, Issue 8, 2003, Pages 2251-2261

  Klein, Christian ^a   Wüstefeld, Torsten ^a   Heinrich, Peter C ^b   Streetz, Konrad L ^a   Manns, Michael P ^a   Trautwein, Christian ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b RWTH AACHEN UNIVERSITY   (Germany)

Author keywords

Concanavalin A; IL 6; Liver failure; T cells; Therapy

Indexed keywords

CELL EXTRACT; CONCANAVALIN A; DNA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; ME 3738; SOYASAPOGENOL A; STAT PROTEIN; TERPENOID DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL NUCLEUS; CONTROLLED STUDY; CORRELATION ANALYSIS; DNA BINDING; DRUG MECHANISM; DRUG STRUCTURE; GENE TARGETING; GENETIC TRANSCRIPTION; LIVER CELL DAMAGE; LIVER FAILURE; LIVER PROTECTION; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INDUCTION;

ACUTE-PHASE REACTION; ANIMALS; CONCANAVALIN A; DNA-BINDING PROTEINS; GENE EXPRESSION; IMMUNOSUPPRESSIVE AGENTS; INTERLEUKIN-6; LIVER FAILURE; MALE; MICE; MICE, INBRED BALB C; MICE, KNOCKOUT; NF-KAPPA B; OLEANOLIC ACID; STAT3 TRANSCRIPTION FACTOR; TRANS-ACTIVATORS; TUMOR NECROSIS FACTOR-ALPHA;

EID: 0041975813     PISSN: 00142980     EISSN: None     Source Type: Journal    
DOI: 10.1002/eji.200323651     Document Type: Article

References (35)

1. Tiegs, G., Hentschel, J. and Wendel, A., A T cell-dependent experimental liver injury in mice inducible by concanavalin A. J. Clin. Invest. 1992. 90: 196-203.
2. Takeda, K., Hayakawa, Y., Van Kaer, L., Matsuda, H., Yagita, H. and Okumura, K., Critical contribution of liver natural killer T cells to a murine model of hepatitis. Proc. Natl. Acad. Sci. USA 2000. 97: 5498-5503.
3. Kaneko, Y., Harada, M., Kawano, T., Yamashita, M., Shibata, Y., Gejyo, F., Nakayama, T. and 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: 105-114.
4. Mizuhara, H., O'Neill, E., Saki, 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 factors and protection by interleukin 6. J. Exp. Med. 1994. 179: 1529-1537.
5. Gantner, F., Leist, M., Lohse, A. W., Germann, P. G. and Tiegs, G., Concanavalin A-induced T cell-mediated hepatic injury in mice: the role of tumor necrosis factor. Hepatology 1995. 21: 190-198.
6. Trautwein, C., Rakemann, T., Brenner, D. A., Streetz, K., Licato, L., Manns, M. P. and Tiegs, G., Concanavalin A-induced liver cell damage: activation of intracellular pathways triggered by tumor necrosis factor in mice. Gastroenterology 1998. 114: 1035-1045.
7. Bozza, M., Bliss, J. L., Maylor, R., Erickson, J., Donnelly, L., Bouchard, P., Dorner, A. J. and Trepicchio, W. L, Interleukin-11 reduces T cell-dependent experimental liver injury in mice. Hepatology 1999. 30: 1441-1447.
8. 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: 26605-26613.
9. Trautwein, C., Rakemann, T., Malek, N. P., Plumpe, J., Tiegs, G. and Manns, M. P., Concanavalin A-induced liver injury triggers hepatocyte proliferation. J. Clin. Invest. 1998. 101: 1960-1969.
10. Kuzuhara, H., Nishiyama, S., Minowa, N., Sasaki, K. and Omoto, S., Protective effects of soyasapogenol A on liver injury mediated by immune response in a concanavalin A-induced hepatitis model. Eur. J. Pharmacol. 2000. 391: 175-181.
11. Chen, R. H., Chang, M. C., Su, Y. H., Tsai, Y. T. and Kuo, M. L., 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: 23013-23019.
12. Kuo, M. L., Chuang, S. E., Lin, M. T. and Yang, S. Y., The involvement of PI 3-K/Akt-dependent up-regulation of Mcl-1 in the prevention of apoptosis of Hep3B cells by interleukin-6. Oncogene 2001. 20: 677-685.
13. Mackiewicz, A., Schooltink, H., Heinrich, P. C. and Rose-John, S., Complex of soluble human IL-6 receptor/IL-6 up-regulates expression of acute-phase proteins. J. Immunol. 1992. 15: 2021-2027.
14. Muller-Newen, G., Kuster, A., Hemmann, U., Keul, R., Horsten, U., Martens, A., Graeve, L., Wijdenes, J. and Heinrich, P. C., Soluble IL-6 receptor potentiates the antagonistic activity of soluble gp130 on IL-6 responses. J. Immunol. 1998. 161: 6347-6355.
15. Schumann, J., Wolf, D., Pahl, A., Brune, K., Papadopoulos, T., Van Rooijen, N. and Tiegs, G., Importance of Kupffer cells for T cell-dependent liver injury in mice. Am. J. Pathol. 2000. 157: 1671-1683.
16. Gregory, S. H., Wing, E. J., Danowski, K. L., Van Rooijen, N., Dyer, K. F. and Tweardy, D. J., IL-6 produced by Kupffer cells induces STAT protein activation in hepatocytes early during the course of systemic listerial infections. J. Immunol. 1998. 160: 6056-6061.
17. Diehl, S., Anguita, J., Hoffmeyer, A., Zapton, T., Ihle, J. N., Fikrig, E. and Rincon, M., Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1. Immunity 2000. 13: 805-815.
18. Narimatsu, M., Maeda, H., Itoh, S., Atsumi, T., Ohtani, T., Nishida, K., Itoh, M., Kamimura, D., Park, S. J., Mizuno, K., Miyazaki, J., Hibi, M., Ishihara, K., Nakajima, K. and Hirano, T., Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells. Mol. Cell. Biol. 2001. 19: 6615-6625.
19. Trautwein, C., Boker, K. and Manns, M. P., Hepatocyte and immune system: acute phase reaction as a contribution to early defence mechanisms. Gut 1994. 35: 1163-1166.
20. Wielockx, B., Lannoy, K., Shapiro, S. D., Itoh, T., Itohara, S., Vandekerckhove, J. and Libert, C., Inhibition of matrix metalloproteinases blocks lethal hepatitis and apoptosis induced by tumor necrosis factor and allows safe antitumor therapy. Nat. Med. 2001. 7: 1202-1208.
21. Steel, D. M. and Whitehead, A. S., The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. Immunol. Today 1994. 15: 81-88.
22. Stix, B., Kahne, T., Sletten, K., Raynes, J., Roessner, A. and Rocken, C., Proteolysis of AA amyloid fibril proteins by matrix metalloproteinases-1, -2, and -3. Am. J. Pathol. 2001. 159: 561-570.
23. Theret, N., Lethi, K., Musso, O. and Clement, B., MMP2 activation by collagenase 1 and concanavalin A in cultured human hepatic stellate cells. Hepatology 1999. 30: 462-468.
24. Wielockx, B., Lannoy, K., Shapidro, S. D., Itosh, T., Itohara, S., Vandereckhove, J. and Libert, C., Inhibition of metalloproteinases blocks lethal hepatitis and apoptosis induced by tumor necrosis factor and allows safe antitumor therapie. J. Exp. Med. 2001. 7: 1202-1208.
25. Doi, T. S., Marino, M. W., Takahashi, T., Yoshida, T., Sakakura, T., Old, L. J. and Obata, Y., Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality. Proc. Natl. Acad. Sci. USA 1999. 6: 2994-2999.
26. Beg, A. A., Sha, W. C., Bronson, R. T., Ghosh, S. and Baltimore, D., Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature 1995. 376: 167-170.
27. DeAngelis, R. A., Kovalovich, K., Cressman, D. E. and Taub, R., Normal liver regeneration in p50/nuclear factor kappaB1 knockout mice. Hepatology 2001. 4: 915-924.
28. Bode, J. G., Fischer, R., Haussinger, D., Graeve, L., Heinrich, P. C. and Schaper, F., The inhibitory effect of IL-1 beta on IL-6-induced alpha 2-macroglobulin expression is due to activation of NF-kappa B. J. Immunol. 2001. 3: 1469-1481.
29. Galun, E., Zeira, E., Pappo, O., Peters, M. and Rose-John, S., Liver regeneration induced by a designer human IL-6/sIL-6R fusion protein reverses severe hepatocellular injury. FASEB J. 2000. 13: 1979-1987.
30. Hecht, N., Pappo, O., Shouval, D., Rose-John, S., Galun, E. and Axelrod, J. H., Hyper-IL-6 gene therapy reverses fulminant hepatic failure. Mol. Ther. 2001. 3: 683-687.
31. Streetz, K., Wuestefeld, T., Leifeld, L., Tacke, F., Graw, A., Kamino, K., Schuetz, G., Mueller, W., Manns, M. P. and Trautwein, C., The role of the IL6/gp130 system for liver disease progression. J. Hepatology 2002. 36 (Suppl. 1): 57A.
32. Rakemann, T., Niehof, M., Kubicka, S., Fischer, M., Manns, M. P., Rose-John, S. and Trautwein, C., The designer cytokine hyper-interleukin-6 is a potent activator of STAT3-dependent gene transcription in vivo and in vitro. J. Biol. Chem. 1999. 274: 1257-1266.
33. Weinhold, B. and Ruther, U., Interleukin-6-dependent and -independent regulation of the human C-reactive protein gene. Biochem. J. 1997. 327: 425-429.
34. Sambrook, J., Fritsch, E. F. and Maniatis, T. (Eds.) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Habor 1989.
35. Niehof, M., Streetz, K., Rakemann, T., Bischoff, S. C., Manns, M. P., Horn, F. and Trautwein, C., Interleukin-6-induced tethering of STAT3 to the LAP/C/EBPbeta promoter suggests a new mechanism of transcriptional regulation by STAT3. J. Biol. Chem. 2001. 276: 9016-9027.