Induction of Mx-2 in rat liver by toxic injury

Background/Aims Mx proteins are supposed to be strictly regulated by viruses or interferon-alpha (IFN-α). We used a non-viral model of acute liver injury to study Mx expression. Methods We induced toxic liver injury by CCl4, and studied the expression of IFN-α, IFN-γ, and IFN-inducible antiviral genes (Mx-2; 2′-5′ oligoadenylate synthetase, 2-5 A; double-stranded RNA-activated protein kinase, PKR). Results Similar to 2-5 A and PKR, Mx-2 gene expression was biphasically induced after CCl4 administration with a maximum at 24 h, and a second peak at 72 h. On protein level, Mx-2 only was up-regulated. IFN-α remained constant for the first 24 h while IFN-γ peaked at 6 h. Thereafter, IFN-α increased to a maximum at 72 h while IFN-γ decreased to 77±4%. Small monocyte-like liver macrophages, but not large macrophages, expressed Mx-2 constitutively. In vitro, IFN-α but not IFN-γ induced Mx-2 in different liver cell populations. IFN-γ, instead, reduced the susceptibility of liver macrophages to the actions of IFN-α. Conclusions Our data suggest that Mx expression does not invariably result from the presence of a viral particle or IFN-α synthesis but may represent an innate defensive armamentarium that may be up-regulated without antigen specificity upon liver injury.