Interleukin-27 acts on hepatic stellate cells and induces signal transducer and activator of transcription 1-dependent responses
1 Department of Biochemistry, University Hospital RWTH-Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
2 Institute of Clinical Chemistry and Pathobiochemistry, University Hospital RWTH-Aachen, Pauwelsstrasse 30, D-52074 Aachen, Germany
3 Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg
Cell Communication and Signaling 2010, 8:19 doi:10.1186/1478-811X-8-19Published: 19 August 2010
Interleukin (IL)-27 is a cytokine belonging to the IL-6/IL-12 cytokine family that is secreted by activated macrophages and dendritic cells and which strongly acts on T-cells and cells of the innate immune system. Not much is known about possible effects of IL-27 on other cell types. It signals via the common IL-6-type-cytokine receptor chain gp130 and the IL-27-specific chain WSX-1. We previously described that IL-27 also stimulates hepatoma cells and primary hepatocytes. The aim of this study was to investigate whether IL-27 would also act on hepatic stellate cells (HSC), the second most abundant hepatic cell type, which would demonstrate a more general role of this cytokine in the liver.
Using a human HSC line and primary rat HSC we investigated the signalling characteristics of IL-27 in these cells. We show that IL-27 activates signal transducer and activator of transcription (STAT) 1 and to a minor extent STAT3 in a human HSC cell line and that it leads to the induction of STAT1 target genes such as interferon response factor-1, myxovirus resistance A and STAT1 itself. Similarly we find that IL-27 also elicits STAT1-dependent responses in primary rat HSC.
We provide the first evidence for a function of IL-27 in HSC and show that its responses resemble Interferon-γ-like functions in these cells. Our data suggests that IL-27 may play an important role in the context of liver inflammation by acting on the different liver cell types.