Oncostatin M: a cytokine upregulated in human cirrhosis, increases collagen production by human hepatic stellate cells

Background/Aims: Hepatic stellate cells are predominantly responsible for the increased extracellular matrix seen in cirrhosis. The cytokine oncostatin M has been implicated in fibrogenesis in vitro in other cell types and in vivo in other tissues, although its effect on hepatic stellate cells or in cirrhosis is unknown. Methods: To examine the effect of oncostatin M on collagen production by human hepatic stellate cells in culture, collagen protein was measured and collagen α2(1) mRNA was quantified by Northern analysis. Tissue inhibitor of metalloproteinase-1 (an inhibitor of collagen degradation) mRNA was measured in response to oncostation M stimulation. To explore the potential biological significance of this work to human liver disease, oncostatin M messenger RNA in normal and cirrhotic human liver was measured. Results: Oncostatin M induced in a 2-fold increase in collagen secretion. The potency of induction of collagen protein secretion was equal to that observed after transforming growth factor β stimulation. An increase in endogenous collagen α2(1) mRNA could not be detected. This suggested a post-transcriptional mechanism for the increase in collagen protein. In response to oncostatin M stimulation, there was a 2-fold increase in the tissue inhibitor or metalloproteinase-1 mRNA. Oncostatin M mRNA was detected in 6/6 cirrhotic livers and 1/7 normal livers after 28 PCR cycles. Conclusion: These results suggest that oncostatin M expression is upregulated in cirrhosis where it may have a role as a profibrogenic cytokine in hepatic stellate cells.