Expression of oncostatin M and its receptors in normal and cirrhotic human liver

Abstract

In the cirrhotic liver, gene expression of the multifunctional cytokine oncostatin M (OSM) is up-regulated, but its cellular origin is unknown. Therefore, we investigated the expression of OSM protein and its specific receptor subunits, OSMRbeta and LIFRbeta in normal and cirrhotic human liver using immunohistochemical and Western blot analysis. OSM protein was expressed in Kupffer cells, variably in normal liver but consistently in cirrhosis. OSMRbeta was expressed at low level in hepatocytes of all normal livers examined, but in no cirrhotic sample. In contrast, LIFRbeta receptor was expressed weakly in normal livers, but much more intensely in cirrhosis, in reactive ductules, bile duct epithelial cells and perisinusoidal areas. Double immunostaining showed co-localization of LIFRbeta with cytokeratin 7, proliferating cell nuclear antigen (PCNA) and leukemia inhibitory factor (LIF), in bile duct epithelial cells, but not with alpha-smooth muscle actin, a myofibroblast marker. In human liver, OSM protein is expressed in Kupffer cells, variably in normals but universally in cirrhosis. The differential expression pattern of OSM and its receptors could allow for differential OSM signaling by alternative utilization of receptors to promote hepatocyte proliferation in acute injury and, with its homologue LIF, for the bile ductular reaction in cirrhosis.