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Brand, Stephan; Dambacher, Julia; Beigel, Florian; Zitzmann, Kathrin; Heeg, Malte H. J.; Weiss, Thomas S.; Prüfer, Thomas; Olszak, Torsten; Steib, Christian J.; Storr, Martin; Göke, Burkhard; Diepolder, Helmut; Bilzer, Manfred; Thasler, Wolfgang E.; Auernhammer, Christoph J.

IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro

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  • Media type: E-Article
  • Title: IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro
  • Contributor: Brand, Stephan; Dambacher, Julia; Beigel, Florian; Zitzmann, Kathrin; Heeg, Malte H. J.; Weiss, Thomas S.; Prüfer, Thomas; Olszak, Torsten; Steib, Christian J.; Storr, Martin; Göke, Burkhard; Diepolder, Helmut; Bilzer, Manfred; Thasler, Wolfgang E.; Auernhammer, Christoph J.
  • imprint: American Physiological Society, 2007
  • Published in: American Journal of Physiology-Gastrointestinal and Liver Physiology
  • Language: English
  • DOI: 10.1152/ajpgi.00239.2006
  • ISSN: 0193-1857; 1522-1547
  • Origination:
  • Footnote:
  • Description: <jats:p>The IL-10-like cytokine IL-22 is produced by activated T cells. In this study, we analyzed the role of this cytokine system in hepatic cells. Expression studies were performed by RT-PCR and quantitative PCR. Signal transduction was analyzed by Western blot experiments and ELISA. Cell proliferation was measured by MTS and [<jats:sup>3</jats:sup>H]thymidine incorporation assays. Hepatocyte regeneration was studied in in vitro restitution assays. Binding of IL-22 to its receptor complex expressed on human hepatic cells and primary human hepatocytes resulted in the activation of MAPKs, Akt, and STAT proteins. IL-22 stimulated cell proliferation and migration, which were both significantly inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin. IL-22 increased the mRNA expression of suppressor of cytokine signaling (SOCS)-3 and the proinflammatory cytokines IL-6, IL-8, and TNF-α. SOCS-1/3 overexpression abrogated IL-22-induced STAT activation and decreased IL-22-mediated liver cell regeneration. Hepatic IL-22 mRNA expression was detectable in different forms of human hepatitis, and hepatic IL-22 mRNA levels were increased in murine T cell-mediated hepatitis in vivo following cytomegalovirus infection, whereas no significant differences were seen in an in vivo model of ischemia-reperfusion injury. In conclusion, IL-22 promotes liver cell regeneration by increasing hepatic cell proliferation and hepatocyte migration through the activation of Akt and STAT signaling, which is abrogated by SOCS-1/3 overexpression.</jats:p>
  • Access State: Open Access