A novel mouse model to study effects of cell-autonomous gp130 activation in the liver

Interleukin 6 (IL-6) is a pleiotropic cytokine involved in inflammation and tissue regeneration. In the liver, IL-6 has been shown to be crucial for the induction of acute-phase proteins, liver regeneration, but also tumour formation. In complex with its cognate IL-6 receptor, IL-6 binds to the signal-transducing subunit gp130. However, little is known about specific effects of IL-6 on particular cell types in the liver. In order to address this question, we recently generated ROSA26-transgenic mice allowing for the Cre-inducible expression of a constitutive active gp130 variant (Lgp130). These mice were bred to Alb-CreERT2, CK19-CreERT2 and LRAT-Cre mice to analyze the effects of ligand-independent gp130 activation in hepatocytes, cholangiocytes and hepatic stellate cells (HSCs). We demonstrate that permanent elevation of acute-phase proteins by hepatocytic gp130 signaling protects from Listeria monocytogenes and Entamoeba histolytica infection. Furthermore, activation of gp130 in HSCs induces paracrine STAT3 activation in hepatocytes. This model allows for the first time the analysis of gp130 signaling in specific cell types of the liver and its impact on the defence against local or systemic infection.