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 t he increased extracellular matrix seen in cirrhosis. The cytokine oncostati n M has been implicated in fibrogenesis in vitro in other cell types and in vice 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 hu man hepatic stellate cells in culture, collagen protein was measured and co llagen alpha 2(1) mRNA was quantified by Northern analysis. Tissue inhibito r of metalloproteinase-1 (an inhibitor of collagen degradation) mRNA was me asured in response to oncostation M stimulation, To explore the potential b iological significance of this work to human liver disease, oncostatin M me ssenger RNA in normal and cirrhotic human liver was measured. Results: Oncostatin M induced in a 2-fold increase in collagen secretion. T he potency of induction of collagen protein secretion was equal to that obs erved after transforming growth factor beta stimulation. An increase in end ogenous collagen alpha 2(1) mRNA could not be detected. This suggested a po st-transcriptional mechanism for the increase in collagen protein. In respo nse 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 upregulat ed in cirrhosis where it may have a role as a profibrogenic cytokine in hep atic stellate cells.