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

Sažetak

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.

Reference

Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med. 2005; 353(12): 1261-1273.

Bergasa NV. Pruritus and fatigue in primary biliary cirrhosis. Clin Liver Dis. 2003; 7: 879-900.

Selmi C, Bowlus CL, Gershwin ME, Coppel RL. Primary biliary cirrhosis. Lancet. 2011; 377: 1600–1609.

Gershwin ME, Mackay IR. The causes of primary biliary cirrhosis: Convenient and inconvenient truths. Hepatology. 2008; 47(2): 737-745.

Hirschfield GM, Gershwin ME. The immunobiology and pathophysiology of primary biliary cirrhosis. Annu Rev Pathol. 2013; 8: 303-330.

Walker JG, Doniach D, Roitt IM, Sherlock S. Serological tests in diagnosis of primary biliary cirrhosis. Lancet 1965; 1: 827–831.

Fussey SP, Guest JR, James OF, Bassendine MF, Yeaman SJ. Identification and analysis of the major M2 autoantigens in primary biliary cirrhosis. Proc. Natl. Acad. Sci. USA 1988; 85: 8654–8658.

Moteki S, Leung PS, Dickson ER, et al. Epitope mapping and reactivity of autoantibodies to the E2 component of 2-oxoglutarate dehydrogenase complex in primary biliary cirrhosis using recombinant 2-oxoglutarate dehydrogenase complex. Hepatology. 1996; 23(3): 436-444.

Miller FW, Alfredsson L, Costenbader KH, et al. Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop. J Autoimmun. 2012; 39(4): 259-271.

Selmi C, Leung PS, Sherr DH, Diaz et al. Mechanisms of environmental influence on human autoimmunity: a National Institute of Environmental Health Sciences expert panel workshop. J Autoimmun. 2012; 39(4): 272-284.

Selmi C, Balkwill DL, Invernizzi P, et al. Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium. Hepatology. 2003; 38(5): 1250-1257.

Mattner J, Savage PB, Leung P, et al. Liver autoimmunity triggered by microbial activation of natural killer T cells. Cell Host Microbe. 2008; 3(5): 304-315.

Rieger R, Leung PS, Jeddeloh MR, et al. Identification of 2-nonynoic acid, a cosmetic component, as a potential trigger of primary biliary cirrhosis. J Autoimmun. 2006; 27(1): 7-16.

Wakabayashi K, Lian ZX, Leung PS, et al. Loss of tolerance in C57BL/6 mice to the autoantigen E2 subunit of pyruvate dehydrogenase by a xenobiotic with ensuing biliary ductular disease. Hepatology. 2008; 48(2): 531-540.

Wakabayashi K, Yoshida K, Leung PS, et al. Induction of autoimmune cholangitis in non-obese diabetic (NOD).1101 mice following a chemical xenobiotic immunization. Clin Exp Immunol. 2009; 155(3): 577-586.

Ambrosini YM, Yang GX, Zhang W, et al. The multi-hit hypothesis of primary biliary cirrhosis: polyinosinic-polycytidylic acid (poly I:C) and murine autoimmune cholangitis. Clin Exp Immunol. 2011; 166(1): 110-120.

Wu SJ, Yang YH, Tsuneyama K, et al. Innate immunity and primary biliary cirrhosis: activated invariant natural killer T cells exacerbate murine autoimmune cholangitis and fibrosis. Hepatology. 2011; 53(3): 915-925.

Gershwin ME, Ansari AA, Mackay IR, et al. Primary biliary cirrhosis: an orchestrated immune response against epithelial cells. Immunol Rev. 2000; 174: 210-225.

Kita H, Matsumura S, He XS, et al. Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis. J Clin Invest. 2002; 109(9): 1231-1240.

Chuang YH, Lan RY, Gershwin ME. The immunopathology of human biliary cell epithelium. Semin Immunopathol. 2009; 31(3): 323-331.

Kimura Y, Leung PS, Kenny TP, et al. Differential expression of intestinal trefoil factor in biliary epithelial cells of primary biliary cirrhosis. Hepatology. 2002; 36(5): 1227-1235.

Lleo A, Invernizzi P, Mackay IR, Prince H, Zhong RQ, Gershwin ME. Etiopathogenesis of primary biliary cirrhosis. World J Gastroenterol. 2008; 14(21): 3328-3337.

Odin JA, Huebert RC, Casciola-Rosen L, LaRusso NF, Rosen A. Bcl-2-dependent oxidation of pyruvate dehydrogenase-E2, a primary biliary cirrhosis autoantigen, during apoptosis. J Clin Invest. 2001; 108(2): 223-232.

Lleo A, Selmi C, Invernizzi P, et al. Apotopes and the biliary specificity of primary biliary cirrhosis. Hepatology. 2009; 49(3): 871-879.

Lleo A, Bowlus CL, Yang GX, et al. Biliary apotopes and anti-mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis. Hepatology. 2010; 52(3): 987-998.

Van de Water J, Gerson LB, Ferrell LD, et al. Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis. Hepatology. 1996; 24(5): 1079-1084.

Van de Water J, Turchany J, Leung PS, et al. Molecular mimicry in primary biliary cirrhosis. Evidence for biliary epithelial expression of a molecule cross-reactive with pyruvate dehydrogenase complex-E2. J Clin Invest. 1993; 91(6): 2653-2664.

Tsuneyama K, Van de Water J, Leung PS, et al. Abnormal expression of the E2 component of the pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before major histocompatibility complex class II and BB1/B7 expression. Hepatology. 1995; 21(4): 1031-1037.

Matsumura S, Van De Water J, Leung P, et al. Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis. Hepatology. 2004; 39(5): 1415-1422.

Kita H, Naidenko OV, Kronenberg M, et al. Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer. Gastroenterology. 2002; 123(4): 1031-1043.

Kita H, Lian ZX, Van de Water J, et al. Identification of HLA-A2-restricted CD8(+) cytotoxic T cell responses in primary biliary cirrhosis: T cell activation is augmented by immune complexes cross-presented by dendritic cells. J Exp Med. 2002; 195(1): 113-123.

Shimoda S, Miyakawa H, Nakamura M, et al. CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis. J Autoimmun. 2008; 31(2): 110-115.

Van de Water J, Ansari A, Prindiville T, et al. Heterogeneity of autoreactive T cell clones specific for the E2 component of the pyruvate dehydrogenase complex in primary biliary cirrhosis. J Exp Med. 1995; 181(2): 723-733.

Oo YH, Weston CJ, Lalor PF, et al. Distinct roles for CCR4 and CXCR3 in the recruitment and positioning of regulatory T cells in the inflamed human liver. J Immunol. 2010; 184(6): 2886-2898.

Lan RY, Cheng C, Lian ZX, et al. Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology. 2006; 43(4): 729-737.

Lan RY, Salunga TL, Tsuneyama K, et al. Hepatic IL-17 responses in human and murine primary biliary cirrhosis. J Autoimmun. 2009; 32(1): 43-51.

Harada K, Isse K, Nakanuma Y. Interferon gamma accelerates NF-kappaB activation of biliary epithelial cells induced by Toll-like receptor and ligand interaction. J Clin Pathol. 2006; 59(2): 184-190.

Shimoda S, Harada K, Niiro H, et al. CX3CL1 (fractalkine): a signpost for biliary inflammation in primary biliary cirrhosis. Hepatology. 2010; 51(2): 567-575.

Chuang YH, Lian ZX, Yang GX, et al. Natural killer T cells exacerbate liver injury in a transforming growth factor beta receptor II dominant-negative mouse model of primary biliary cirrhosis. Hepatology. 2008; 47(2): 571-580.

Krams SM, Dorshkind K, Gershwin ME. Generation of biliary lesions after transfer of human lymphocytes into severe combined immunodeficient (SCID) mice. J Exp Med. 1989; 170(6): 1919-1930.

Irie J, Wu Y, Wicker LS, et al. NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and pathogenetically models human primary biliary cirrhosis. J Exp Med. 2006; 203(5): 1209-1219.

Oertelt S, Lian ZX, Cheng CM, et al. Anti-mitochondrial antibodies and primary biliary cirrhosis in TGF-beta receptor II dominant-negative mice. J Immunol. 2006; 177(3): 1655-1660.

Wakabayashi K, Lian ZX, Moritoki Y, et al. IL-2 receptor alpha(-/-) mice and the development of primary biliary cirrhosis. Hepatology. 2006; 44(5): 1240-1249.

Hsu W, Zhang W, Tsuneyama K, et al. Differential mechanisms in the pathogenesis of autoimmune cholangitis versus inflammatory bowel disease in interleukin-2Ralpha(-/-) mice. Hepatology. 2009; 49(1): 133-140.

Amano K, Leung PS, Rieger R, et al. Chemical xenobiotics and mitochondrial autoantigens in primary biliary cirrhosis: identification of antibodies against a common environmental, cosmetic, and food additive, 2-octynoic acid. J Immunol. 2005; 174(9): 5874-5883.

Naiyanetr P, Butler JD, Meng L, et al. Electrophile-modified lipoic derivatives of PDC-E2 elicits anti-mitochondrial antibody reactivity. J Autoimmun. 2011; 37(3): 209-216.

Rieger R, Leung PS, Jeddeloh MR, et al. Identification of 2-nonynoic acid, a cosmetic component, as a potential trigger of primary biliary cirrhosis. J Autoimmun. 2006; 27(1): 7-16.

Leung PS, Park O, Tsuneyama K, et al. Induction of primary biliary cirrhosis in guinea pigs following chemical xenobiotic immunization. J Immunol. 2007; 179(4): 2651-2657.

Leung PS, Quan C, Park O, et al. Immunization with a xenobiotic 6-bromohexanoate bovine serum albumin conjugate induces antimitochondrial antibodies. J Immunol. 2003; 170(10): 5326-5332.