Xenobiotic Induced Model of Primary Biliary Cirrhosis

Aleksandar Arsenijevic; Jelena Milovanovic; Bojana Stojanovic; Marija Milovanovic; Eric Gershwin; Patrick Leung; Nebojsa Arsenijevic; Miodrag L Lukic

doi:10.5937/sjecr15-6270

Aleksandar Arsenijevic Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac
Jelena Milovanovic Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac
Bojana Stojanovic Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac
Marija Milovanovic Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac
Eric Gershwin Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA
Patrick Leung Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA
Nebojsa Arsenijevic Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac
Miodrag L Lukic Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac

DOI: https://doi.org/10.5937/sjecr15-6270

Abstract

Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver characterized by destruction of the intrahepatic bile ducts and the presence of antimitochondrial antibodies (AMAs). Several murine models of PBC with similar serological, biochemical, and histological features to human PBC have been developed in the recent years. These animal models enabled the investigation of the etiology and mechanisms involved in the pathogenesis of PBC. Immune response in PBC is directed towards E2 components of the 2-oxo-acid dehydrogenase family of enzymes located in mitochondria and immunodominant epitope is a lipoylated peptide sequence shared by these enzymes. Immunization of mice with 2-octynoic acid coupled to bovine serum albumin (2-OA-BSA), an antigen structurally related to the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), recapitulates the histologucal features of human PBC. This model of xenobiotic induced PBC is suitable for exploring the early events in PBC pathogenesis and for developing new therapeutics for PBC.

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