There has been growing evidence that IL-6 is protective against many pathophysiological conditions in the liver. IL-6 is a protein called a cytokine, which has cell protective functions. In cells, IL-6 acts by binding to a specific receptor in the cell membrane, which then triggers activation of gp130, a signal transducing protein. Gp130 leads to the activation of a signaling pathway inside cells from the membrane to the nucleus called the Jak/Stat pathway.
The researchers used rodent models of liver damage that causes hepatitis and liver damage involving immune T cells. Their aim was to characterize mechanisms involved in mediating IL-6-–dependent protection. They demonstrate that IL-6/gp130/Stat3–dependent expression of two proteins in liver cells – KC and SAA2 – is essential in mediating the protective effect of IL-6.
This establishes the role of key protective factors in liver injury mediated by hepatitis and immune mechanisms. KC and SAA2 are two proteins that may be of interest in developing therapies to treat immune-mediated liver disease in humans.
TITLE: The IL-6-gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-–mediated liver injury
AUTHOR CONTACT:
Christian Klein
Hannover Medical School, Hannover, Germany
Phone: 049 511 5323401; Fax: 49-511-532-5692; E-mail: klein.christian@mh-hannover.de
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Journal of Clinical Investigation