Different effects of rat interferon alpha, beta and gamma on rat hepatic stellate cell proliferation and activation

Liver fibrosis is the common sequel of chronic liver diseases. Recent studies have identified hepatic stellate cells as the primary cell type mediating hepatic fibrogenesis. It has been demonstrated that hepatic stellate cells undergo a process of activation during the development of liver fibrosis. During the activation process, hepatic stellate cells acquire myofibroblast-like phenotype featuring the expression of smooth muscle alpha actin. Interferons have been employed for the treatment of viral hepatitis. However, it is unclear what is the effect of interferons on the prevention and treatment of liver fibrosis. Moreover, it is not clear whether there are any differences among interferon alpha, interferon beta, and interferon gamma in the treatment of liver fibrosis. Therefore, our objective in current study is to investigate the effects of rat interferon-alpha, interferon-beta, and interferon-gamma on the proliferation and activation of rat hepatic stellate cells.

Rat interferon-beta and interferon-gamma significantly inhibited rat hepatic stellate cell proliferation while rat interferon-alpha did not affect the cell proliferation under the same culture condition. Inhibition of cell proliferation was confirmed by both WST-1 cell proliferation assay and 5-bromo-2'-deoxy-uridine incorporation assay. Similar results were observed regarding interferons regulation of hepatic stellate cell activation. Both rat interferon-beta and interferon-gamma reduced smooth muscle alpha-actin abundance after 6 days treatment, but rat interferon-alpha did not alter smooth muscle alpha-actin level.

Our results indicate that rat interferon-alpha and interferon-beta have different biological effects on rat hepatic stellate cells and suggest that there are different signaling events between interferon-alpha and interferon-beta in hepatic stellate cells.