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Early development of primary biliary cirrhosis in female C57BL/6 mice because of poly I:C administration

Authors


Morikazu Onji, MD, Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Toon-shi, Ehime 791-0295, Japan
Tel: +81-89-960-5308
Fax: +81-89-960-5310
e-mail: onjimori@m.ehime-u.ac.jp

Abstract

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-α was estimated in the sera by an ELISA method. Poly I:C injection induced IFN-α.

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.

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