Early development of primary biliary cirrhosis in female C57BL/6 mice because of poly I:C administration.
BACKGROUND
Primary biliary cirrhosis (PBC) is one of the organ-specific autoimmune diseases characterized by destruction of the biliary epithelial cells, cholestasis, liver cirrhosis, and liver failure. With the postulation that induction of the autoimmune process might induce PBC-like cholangitis, here we used polyinosinic polycytidylic acid (poly I:C), an inducer of type-1 interferon (IFN), to generate an autoimmune cholangitis animal model.


METHODS
Female C57BL/6 mice were injected with 5 mg/kg of poly I:C twice a week for 28 consecutive weeks. Liver specimens were collected to evaluate the degree of cell infiltration. Autoantibodies, including antimitochondrial antibody (AMA), were assayed by immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. IFN-alpha was estimated in the sera by an ELISA method. Poly I:C injection induced IFN-alpha.


RESULTS
Mononuclear cells were detected at the portal areas 8 weeks after the start of poly I:C injection, which progressed up to 16 weeks. Autoantibodies, including AMA, were detected in the sera from all poly I:C-injected mice.


CONCLUSIONS
In conclusion, we show an early development of a PBC-like cholangitis in a genetically susceptible mouse strain because of poly I:C administration. This model would be helpful to study PBC immunopathogenesis and to evaluate the effectiveness of newly developed therapeutic regimens for PBC.
Okada
Chizuko
C
Third Department of Internal Medicine, Ehime University School of Medicine, Toon-shi, Ehime, Japan.
Akbar
Sk Md Fazle
SM
Horiike
Norio
N
Onji
Morikazu
M
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007369:Interferon Inducers / Q000494:pharmacology*; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000494:pharmacology*
D001323:Autoantibodies; D007369:Interferon Inducers; D007370:Interferon Type I; D016898:Interferon-alpha; D011070:Poly I-C