Induction of Mx-2 in rat liver by toxic injury.
OBJECTIVE
Mx proteins are supposed to be strictly regulated by viruses or interferon-alpha (IFN-alpha). We used a non-viral model of acute liver injury to study Mx expression.


METHODS
We induced toxic liver injury by CCl(4), and studied the expression of IFN-alpha, IFN-gamma, 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 CCl(4) administration with a maximum at 24 h, and a second peak at 72 h. On protein level, Mx-2 only was up-regulated. IFN-alpha remained constant for the first 24 h while IFN-gamma peaked at 6 h. Thereafter, IFN-alpha increased to a maximum at 72 h while IFN-gamma decreased to 77+/-4%. Small monocyte-like liver macrophages, but not large macrophages, expressed Mx-2 constitutively. In vitro, IFN-alpha but not IFN-gamma induced Mx-2 in different liver cell populations. IFN-gamma, instead, reduced the susceptibility of liver macrophages to the actions of IFN-alpha.


CONCLUSIONS
Our data suggest that Mx expression does not invariably result from the presence of a viral particle or IFN-alpha synthesis but may represent an innate defensive armamentarium that may be up-regulated without antigen specificity upon liver injury.
Batusic
Danko S
DS
Division of Gastroenterology and Endocrinology, Department of Medicine, Georg-August-University Göttingen, Robert-Koch-Strasse 40, Göttingen 37075, Germany.
Armbrust
Thomas
T
Saile
Bernhard
B
Ramadori
Giuliano
G
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000150:complications*; D002469:Cell Separation; D056486:Chemical and Drug Induced Liver Injury; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016898:Interferon-alpha / Q000378:metabolism / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007372:Interferons / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D064547:Myxovirus Resistance Proteins; D010586:Phagocytes / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019892:eIF-2 Kinase / Q000378:metabolism
D016898:Interferon-alpha; C579066:Mx2 protein, rat; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D007371:Interferon-gamma; D007372:Interferons; D019892:eIF-2 Kinase; D019204:GTP-Binding Proteins