| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
LIVER AND BILIARY TRACT
1Department of Medicine II and 2Department of Surgery, University-Hospital Munich-Grosshadern and University of Munich, Munich; and 3Center for Liver Cell Research, University Hospital Regensburg, Regensburg, Germany
Submitted 1 June 2006 ; accepted in final form 20 December 2006
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 [3H]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-
. 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.
interleukin-10-like cytokines; liver regeneration; cell migration; suppressor of cytokine signaling
This article has been cited by other articles:
|
|
 |
|
  B. Gao, S. Radaeva, and O. Park Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases J. Leukoc. Biol., September 1, 2009; 86(3): 513 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Dambacher, F Beigel, K Zitzmann, E N De Toni, B Goke, H M Diepolder, C J Auernhammer, and S Brand The role of the novel Th17 cytokine IL-26 in intestinal inflammation Gut, September 1, 2009; 58(9): 1207 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Brand Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease Gut, August 1, 2009; 58(8): 1152 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhang, Y. Chen, H. Wei, C. Zheng, R. Sun, J. Zhang, and Z. Tian Antiapoptotic Activity of Autocrine Interleukin-22 and Therapeutic Effects of Interleukin-22-Small Interfering RNA on Human Lung Cancer Xenografts Clin. Cancer Res., October 15, 2008; 14(20): 6432 - 6439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dambacher, F. Beigel, J. Seiderer, D. Haller, B. Goke, C. J Auernhammer, and S. Brand Interleukin 31 mediates MAP kinase and STAT1/3 activation in intestinal epithelial cells and its expression is upregulated in inflammatory bowel disease Gut, September 1, 2007; 56(9): 1257 - 1265. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
