Ligand-independent IL-6 pathway activation (L-gp130) accelerates the transformation of proliferating human hepatocytes via increased oxidative stress in comparison to ligand-dependent IL-6 pathway activation (Hyper-IL-6)
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Konstitutive gp-130-Aktivierung beschleunigt die Transformation von proliferierenden humanen Hepatozyten durch oxidativen Stress im Vergleich zu Hyper-IL-6-Aktivierung
Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky
Erscheinungsjahr:
2015
Medientyp:
Text
Schlagworte:
IL-6
hepatocytes
oxidative stress
Hyper-IL-6
610 Medizin, Gesundheit
44.87 Gastroenterologie
ddc:610
Beschreibung:
In the context of chronic liver injury, pro-inflammatory signaling pathways and reactive oxygen species (ROS) promote hepatocyte transformation. Recently, interleukin 6 (IL-6) signaling has been established as an independent risk factor for HCC in patients with chronic hepatitis C. In addition, somatic gain-of-function mutations in the IL-6 signal transducer glycoprotein 130 (gp130) were found in 60% of inflammatory hepatocellular adenomas, benign liver lesions with high risk for transformation. However, the detailed mechanistic interactions between IL-6 signaling and oncogenic oxidative stress as driver for downstream transformation events are still unidentified. To elucidate these mechanisms, we activated gp130 in untransformed hTERT-immortalized human fetal hepatocytes (FH-hTERT) and challenged the cells with ROS. Additionally, we activated IL-6 trans-signaling with the designer cytokine Hyper-IL-6 to compare ligand-independent with ligand-dependent IL-6 signaling.