JCI - The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell

The IL-6–gp130–STAT3 pathway in hepatocytes triggers liver protection in T cell–mediated liver injury

Christian Klein, Torsten Wüstefeld, Ulrike Assmus, Tania Roskams, Stefan Rose-John, Michael Müller, Michael P. Manns, Mattias Ernst, Christian Trautwein

Published in Volume 115, Issue 4

J Clin Invest. 2005; 115(4):860–869 doi:10.1172/JCI23640

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Figure 5

gp130-STAT3 signaling in hepatocytes is responsible for IL-6–induced liver protection. Con A–induced hepatitis was induced by intravenous injection of 32.5 mg/kg Con A in hepatocyte-specific gp130^ΔSTAT (alfpCre gp130^ΔSTAT/LoxP) and hepatocyte-specific gp130^Y757F/LoxP mice (alfpCre gp130^Y757F/LoxP). Mice were pretreated 3 hours before Con A injection with NaCl (solid line) or IL-6 (200 ng/g) (dotted line) by i.p. injection. (A and B) Liver damage was quantified by detection of ASTs. (A) AST levels of alfpCre gp130^Y757F/LoxPmice in the time course of Con A–induced hepatitis, pretreated with NaCl (solid line) or IL-6 (dotted line). ^#P < 0.01 and *P < 0.05 vs. corresponding IL-6–pretreated control group at the same time point. (B) AST levels of alfpCre gp130^ΔSTAT/LoxP in the time course of Con A–induced hepatitis, pretreated with NaCl (solid line) or IL-6 (dotted line). (C and D) TNF-α, IFN-γ, and IL-6 secretion in the serum during Con A–induced hepatitis in alfpCre gp130^Y757F/LoxP (C) and alfpCre gp130^ΔSTAT/LoxP mice (D) was determined by ELISA. ^§P < 0.001 vs. corresponding IL-6–pretreated alfpCre gp130^Y757F/LoxP mice at the same time point.