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

Rat interferon-β and interferon-γ significantly inhibited rat hepatic stellate cell proliferation while rat interferon-α 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-β and interferon-γ reduced smooth muscle α-actin abundance after 6 days treatment, but rat interferon-α did not alter smooth muscle α-actin level.Our results indicate that rat interferon-α and interferon-β have different biological effects on rat hepatic stellate cells and suggest that there are different signaling events between interferon-α and interferon-β in hepatic stellate cells.Liver fibrosis is the common sequel of chronic liver injury of variable origin (viral infection, metabolic diseases and toxin). Recent studies have identified hepatic stellate cells (HSCs) as the primary cell type mediating hepatic fibrosis [1,2]. In normal liver, HSCs are the site of storage and metabolism of vitamin A [3,4]. During hepatic fibrogenesis, HSCs proliferate and undergo a process of activation, developing a myofibroblast-like appearance. Activated HSCs appear to lose lipid droplet, increase rough endoplasmic reticulum, and express smooth muscle alpha actin (SMA) [5-7]. Activated HSCs also increase the synthesis of extracellular matrix components that form the major part of the fibrotic liver [8,9].Interferons were first discovered as anti-viral soluble protein and at present, interferon-α is the main medication for the treatment of viral hepatitis [10,11]. Interferons consist of type 1 interferon, which includes interferon-α, -β and -ω, and type II interferon, which is interferon γ. Several subtypes are observed in human interferon. Interferon-α has at least 14 subtypes, interferon-β has 3 subtypes and interferon-γ has 5 subtypes [