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IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2007 Apr; Vol. 292 (4), pp. G1019-28. Date of Electronic Publication: 2007 Jan 04. - Publication Year :
- 2007
-
Abstract
- 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 [(3)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-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.
- Subjects :
- Animals
Cell Culture Techniques
Cell Line, Tumor
Cell Movement
Cell Proliferation
Disease Models, Animal
Dose-Response Relationship, Drug
Extracellular Signal-Regulated MAP Kinases metabolism
Hepatectomy
Hepatitis metabolism
Hepatocytes drug effects
Humans
Inflammation Mediators metabolism
Interleukins pharmacology
Liver cytology
Liver surgery
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinases metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
RNA, Messenger metabolism
Receptors, Interleukin genetics
Receptors, Interleukin metabolism
STAT Transcription Factors metabolism
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins genetics
T-Lymphocytes metabolism
Time Factors
Transfection
Up-Regulation
Interleukin-22
Hepatocytes metabolism
Interleukins metabolism
Liver metabolism
Liver Regeneration
Signal Transduction drug effects
Suppressor of Cytokine Signaling Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1857
- Volume :
- 292
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 17204547
- Full Text :
- https://doi.org/10.1152/ajpgi.00239.2006