Hepatocytes response to interferon alpha levels recorded after liver resection

Extensive damage of liver parenchyma stimulates hepatic cells to transit from quiescence to proliferation with eventual restoration of liver mass and function. Our recent studies have revealed upregulated expression of interferon (IFN)-α and its antiviral activity during the early hours after partial hepatectomy. In this study, we analyzed the response of primary hepatocytes from intact liver to IFN-α mimicking its levels (250 U/mL) during the transition period of liver restoration. The gene expression profile was analyzed with rat genome array 230 2.0 (Affymetrix). After 3- and 6-h treatment we identified respectively 28 and 124 differentially expressed genes responsible for autonomous changes in hepatocytes and those involving non-parenchymal cells in a concerted response to IFN-α. The response has an energy sparing character and affects all levels of gene expression. The factors activating T cells and apoptosis are opposed by those restricting the signal propagation, inhibiting T cells activation, and promoting survival. The partial resemblance between the specific in vitro response to IFN-α and the processes in regenerating liver is discussed. Our study opens the way to a more focused investigation of the liver cell response to quasiphysiological dose of IFN-α.