Interferon-β Mediates Signaling Pathways Uniquely Regulated in Hepatic Stellate Cells and Attenuates the Progression of Hepatic Fibrosis in a Dietary Mouse Model

The results of clinical and experimental studies suggest that type I interferons (IFNs) may have direct antifibrotic activity in addition to their antiviral properties. However, the mechanisms are still unclear; in particular, little is known about the antifibrotic activity of IFN-β and how its activity is distinct from that of IFN-α. Using DNA microarrays, we demonstrated that gene expression in TWNT-4 cells, an activated human hepatic stellate cell line, was remarkably altered by IFN-β more than by IFN-α. Integrated pathway enrichment analyses revealed that a variety of IFN-β–mediated signaling pathways are uniquely regulated in TWNT-4 cells, including those related to cell cycle and Toll-like receptor 4 (TLR4) signaling. To investigate the antifibrotic activity of IFN-β and the involvement of TLR4 signaling in vivo, we used mice fed a choline-deficient l-amino acid-defined diet as a model of nonalcoholic steatohepatitis-related hepatic fibrosis. In this model, the administration of IFN-β significantly ...