Journal of Hepatology
Volume 51, Issue 6 , Pages 1037-1045 , December 2009

Toll-like receptor activated human and murine hepatic stellate cells are potent regulators of hepatitis C virus replication

  • Bo Wang

      Affiliations

    • Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany
    • Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • ,
  • Martin Trippler

      Affiliations

    • Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany
  • ,
  • Rongjuan Pei

      Affiliations

    • Institute of Virology, University Hospital of Essen, Essen, Germany
  • ,
  • Mengji Lu

      Affiliations

    • Institute of Virology, University Hospital of Essen, Essen, Germany
  • ,
  • Ruth Broering

      Affiliations

    • Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany
  • ,
  • Guido Gerken

      Affiliations

    • Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany
  • ,
  • Joerg F. Schlaak

      Affiliations

    • Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 201 7232518; fax: +49 201 7235749.

Received 27 January 2009 ,Revised 3 June 2009 ,Accepted 23 June 2009.

References 

  1. Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology. 2008;134:1655–1669
  2. Parsons CJ, Takashima M, Rippe RA. Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol. 2007;22:S79–S84
  3. Ikeda M, Kato N. Life style-related diseases of the digestive system: cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: suppression of HCV replication by statins and synergistic action with interferon. J Pharmacol Sci. 2007;105:145–150
  4. Schulze-Krebs A, Preimel D, Popov Y, Bartenschlager R, Lohmann V, Pinzani M, et al. Hepatitis C virus-replicating hepatocytes induce fibrogenic activation of hepatic stellate cells. Gastroenterology. 2005;129:246–258
  5. Isogawa M, Robek MD, Furuichi Y, Chisari FV. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol. 2005;79:7269–7272
  6. Horsmans Y, Berg T, Desager JP, Mueller T, Schott E, Fletcher SP, et al. Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection. Hepatology. 2005;42:724–731
  7. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4:499–511
  8. Colonna M. TLR pathways and IFN-regulatory factors: to each its own. Eur J Immunol. 2007;37:306–309
  9. Kawai T, Akira S. TLR signaling. Semin Immunol. 2007;19:24–32
  10. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004;5:730–737
  11. Kitamura Y, Tanigawa T, Katsumoto T, Tomita K, Wang HR, Hirai K, et al. Cell growth and differentiation of a novel mouse Ito (fat-storing) cell line transformed by a temperature-sensitive mutant of simian virus 40. Hepatology. 1997;26:323–329
  12. Paik YH, Schwabe RF, Bataller R, Russo MP, Jobin C, Brenner DA. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology. 2003;37:1043–1055
  13. Xu L, Hui AY, Albanis E, Arthur MJ, O’Byrne SM, Blaner WS, et al. Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut. 2005;54:142–151
  14. Broering R, Wu J, Meng Z, Hilgard P, Lu M, Trippler M, et al. Toll-like receptor-stimulated non-parenchymal liver cells can regulate hepatitis C virus replication. J Hepatol. 2008;48:914–922
  15. Krieger N, Lohmann V, Bartenschlager R. Enhancement of hepatitis C virus RNA replication by cell culture-adaptive mutations. J Virol. 2001;75:4614–4624
  16. Mujtaba MG, Patel CB, Patel RA, Flowers LO, Burkhart MA, Waiboci LW, et al. The gamma interferon (IFN-gamma) mimetic peptide IFN-gamma (95–133) prevents encephalomyocarditis virus infection both in tissue culture and in mice. Clin Vaccine Immunol. 2006;13:944–952
  17. Katze MG, He Y, Gale M. Viruses and interferon: a fight for supremacy. Nat Rev Immunol. 2002;2:675–687
  18. Seki E, Brenner DA. Toll-like receptors and adaptor molecules in liver disease: update. Hepatology. 2008;48:322–325
  19. Paik YH, Schwabe RF, Bataller R, Russo MP, Jobin C, Brenner DA. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology. 2003;37:1043–1055
  20. Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA, et al. TLR 4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 2007;13:1324–1332
  21. Watanabe A, Hashmi A, Gomes DA, Town T, Badou A, Flavell RA, et al. Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9. Hepatology. 2007;46:1509–1518
  22. Herrmann J, Gressner AM, Weiskirchen R. Immortal hepatic stellate cell lines: useful tools to study hepatic stellate cell biology and function. J Cell Mol Med. 2007;11:704–722
  23. Wu J, Lu M, Meng Z, Trippler M, Broering R, Szczeponek A, et al. Toll-like receptor-mediated control of HBV replication by nonparenchymal liver cells in mice. Hepatology. 2007;46:1769–1778
  24. Wu J, Meng Z, Min J, Pei R, Trippler M, Broering R, et al. HBV suppresses Toll-like receptor mediated innate immune responses in murine parenchymal and non-parenchymal liver cells. Hepatology. 2009;49:1132–1140
  25. Bataller R, Paik YH, Lindquist JN, Lemasters JJ, Brenner DA. Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells. Gastroenterology. 2004;126:529–540
  26. Shin JY, Hur W, Wang JS, Jang JW, Kim CW, Bae SH, et al. HCV core protein promotes liver fibrogenesis via up-regulation of CTGF with TGF-beta1. Exp Mol Med. 2005;37:138–145
  27. Viñas O, Bataller R, Sancho-Bru P, Ginès P, Berenguer C, Enrich C, et al. Human hepatic stellate cells show features of antigen-presenting cells and stimulate lymphocyte proliferation. Hepatology. 2003;38:919–929
  28. Schuppan D, Krebs A, Bauer M, Hahn EG. Hepatitis C and liver fibrosis. Cell Death Differ. 2003;10:S59–S67
  29. Jeong WI, Park O, Radaeva S, Gao B. STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity. Hepatology. 2006;44:1441–1451
  30. Targett-Adams P, Boulant S, McLauchlan J. Visualization of double-stranded RNA in cells supporting hepatitis C virus RNA replication. J Virol. 2008;82:2182–2195

 The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.

PII: S0168-8278(09)00473-5

doi: 10.1016/j.jhep.2009.06.020

Journal of Hepatology
Volume 51, Issue 6 , Pages 1037-1045 , December 2009