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

被引:93
作者
Brand, Stephan
Dambacher, Julia
Beigel, Florian
Zitzmann, Kathrin
Heeg, Malte H. J.
Weiss, Thomas S.
Pruefer, Thomas
Olszak, Torsten
Steib, Christian J.
Storr, Martin
Goeke, Burkhard
Diepolder, Helmut
Bilzer, Manfred
Thasler, Wolfgang E.
Auernhammer, Christoph J.
机构
[1] Univ Hosp Munich Grosshadern, Dept Med 2, D-81377 Munich, Germany
[2] Univ Hosp Munich Grosshadern, Dept Surg, D-81377 Munich, Germany
[3] Univ Munich, Munich, Germany
[4] Univ Hosp Regensburg, Ctr Liver Cell Res, Regensburg, Germany
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2007年 / 292卷 / 04期
关键词
interleukin-10-like cytokines; liver regeneration; cell migration; suppressor of cytokine signaling;
D O I
10.1152/ajpgi.00239.2006
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 [H-3] 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-alpha. 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.
引用
收藏
页码:G1019 / G1028
页数:10
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