Role of cholangiocytes in primary biliary cirrhosis

Seminars in Liver Disease

Volumn 34, Issue 3, 2014, Pages 273-284

  Lleo, Ana ^a   Maroni, Luca ^b   Glaser, Shannon ^c,d,e   Alpini, Gianfranco ^c,d,e   Marzioni, Marco ^b  

^a HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^b UNIVERSITÀ POLITECNICA DELLE MARCHE   (Italy)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

^d SCOTT AND WHITE MEMORIAL HOSPITAL   (United States)

^e TEXAS A M COLLEGE OF MEDICINE   (United States)

Author keywords

apoptosis; cholangiocytes; intrahepatic bile ducts; mitochondrial antigens

Indexed keywords

CHROMOGRANIN A; ESTROGEN RECEPTOR BETA; IMMUNOGLOBULIN A; TOLL LIKE RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; VASCULOTROPIN; VASCULOTROPIN RECEPTOR;

ARTICLE; BILE DUCT; BILE SECRETION; CELL PROLIFERATION; CELL SURVIVAL; HEPATOBILIARY SYSTEM; HUMAN; IMMUNOBIOLOGY; INTRAHEPATIC CHOLESTASIS; LIVER INJURY; NONHUMAN; PRIMARY BILIARY CIRRHOSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; ANIMAL; APOPTOSIS; AUTOIMMUNITY; BILIARY CIRRHOSIS; DISEASE MODEL; EPITHELIUM CELL; IMMUNOLOGY; INTRAHEPATIC BILE DUCT; METABOLISM; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; AUTOIMMUNITY; BILE DUCTS, INTRAHEPATIC; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; EPITHELIAL CELLS; HUMANS; LIVER CIRRHOSIS, BILIARY; SIGNAL TRANSDUCTION;

EID: 84904993151     PISSN: 02728087     EISSN: 10988971     Source Type: Journal    
DOI: 10.1055/s-0034-1383727     Document Type: Article

References (136)

1. Kaplan M. M., Gershwin M. E. Primary biliary cirrhosis. N Engl J Med: 2005; 353 12 1261 1273
2. Gershwin M. E., Mackay I. R. The causes of primary biliary cirrhosis: Convenient and inconvenient truths. Hepatology: 2008; 47 2 737 745
3. Invernizzi P. Future directions in genetic for autoimmune diseases. J Autoimmun: 2009; 33 1 1 2
4. Invernizzi P., Gershwin M. E. Primary biliary cirrhosis: bad genes, bad luck. Dig Dis Sci: 2012; 57 3 599 601
5. Syal G., Fausther M., Dranoff J. A. Advances in cholangiocyte immunobiology. Am J Physiol Gastrointest Liver Physiol: 2012; 303 10 G1077 G1086
6. Odin J. A., Huebert R. C., Casciola-Rosen L., LaRusso N. F., 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
7. Lleo A., Selmi C., Invernizzi P., et al. Apotopes and the biliary specificity of primary biliary cirrhosis. Hepatology: 2009; 49 3 871 879
8. Lleo A., Bowlus C. L., Yang G. X., et al. Biliary apotopes and anti-mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis. Hepatology: 2010; 52 3 987 998
9. Carbone M., Mells G. F., Alexander G. J., et al. Calcineurin inhibitors and the IL12A locus influence risk of recurrent primary biliary cirrhosis after liver transplantation. Am J Transplant: 2013; 13 4 1110 1111
10. Ludwig J. New concepts in biliary cirrhosis. Semin Liver Dis: 1987; 7 4 293 301
11. Kanno N., LeSage G., Glaser S., Alvaro D., Alpini G. Functional heterogeneity of the intrahepatic biliary epithelium. Hepatology: 2000; 31 3 555 561
12. Alpini G., Glaser S., Robertson W., et al. Large but not small intrahepatic bile ducts are involved in secretin-regulated ductal bile secretion. Am J Physiol: 1997; 272 5 Pt 1 G1064 G1074
13. Alpini G., Roberts S., Kuntz S. M., et al. Morphological, molecular, and functional heterogeneity of cholangiocytes from normal rat liver. Gastroenterology: 1996; 110 5 1636 1643
14. Benedetti A., Bassotti C., Rapino K., Marucci L., Jezequel A. M. A morphometric study of the epithelium lining the rat intrahepatic biliary tree. J Hepatol: 1996; 24 3 335 342
15. Marzioni M., Glaser S. S., Francis H., Phinizy J. L., LeSage G., Alpini G. Functional heterogeneity of cholangiocytes. Semin Liver Dis: 2002; 22 3 227 240
16. Glaser S., Francis H., Demorrow S., et al. Heterogeneity of the intrahepatic biliary epithelium. World J Gastroenterol: 2006; 12 22 3523 3536
17. Ueno Y., Alpini G., Yahagi K., et al. Evaluation of differential gene expression by microarray analysis in small and large cholangiocytes isolated from normal mice. Liver Int: 2003; 23 6 449 459
18. Beuers U., Hohenester S., de Buy Wenniger L. J., Kremer A. E., Jansen P. L., Elferink R. P. The biliary HCO(3)(-) umbrella: a unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies. Hepatology: 2010; 52 4 1489 1496
19. Marinelli R. A., Tietz P. S., Pham L. D., Rueckert L., Agre P., LaRusso N. F. Secretin induces the apical insertion of aquaporin-1 water channels in rat cholangiocytes. Am J Physiol: 1999; 276 1 Pt 1 G280 G286
20. Kanno N., LeSage G., Glaser S., Alpini G. Regulation of cholangiocyte bicarbonate secretion. Am J Physiol Gastrointest Liver Physiol: 2001; 281 3 G612 G625
21. Martínez-Ansó E., Castillo J. E., Díez J., Medina J. F., Prieto J. Immunohistochemical detection of chloride/bicarbonate anion exchangers in human liver. Hepatology: 1994; 19 6 1400 1406
22. Strazzabosco M., Mennone A., Boyer J. L. Intracellular pH regulation in isolated rat bile duct epithelial cells. J Clin Invest: 1991; 87 5 1503 1512
23. Banales J. M., Arenas F., Rodríguez-Ortigosa C. M., et al. Bicarbonate-rich choleresis induced by secretin in normal rat is taurocholate-dependent and involves AE2 anion exchanger. Hepatology: 2006; 43 2 266 275
24. Glaser S. S., Gaudio E., Rao A., et al. Morphological and functional heterogeneity of the mouse intrahepatic biliary epithelium. Lab Invest: 2009; 89 4 456 469
25. Medina J. F., Martínez-Ansó, Vazquez J. J., Prieto J. Decreased anion exchanger 2 immunoreactivity in the liver of patients with primary biliary cirrhosis. Hepatology: 1997; 25 1 12 17
26. Melero S., Spirlì C., Zsembery A., et al. Defective regulation of cholangiocyte Cl-/HCO3(-) and Na+/H+ exchanger activities in primary biliary cirrhosis. Hepatology: 2002; 35 6 1513 1521
27. Beuers U., Maroni L., Elferink R. O. The biliary HCO(3)(-) umbrella: experimental evidence revisited. Curr Opin Gastroenterol: 2012; 28 3 253 257
28. Hohenester S., Wenniger L. M., Paulusma C. C., et al. A biliary HCO3- umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes. Hepatology: 2012; 55 1 173 183
29. Banales J. M., Sáez E., Uriz M., et al. Up-regulation of microRNA 506 leads to decreased Cl-/HCO3- anion exchanger 2 expression in biliary epithelium of patients with primary biliary cirrhosis. Hepatology: 2012; 56 2 687 697
30. Alpini G., Glaser S. S., Ueno Y., et al. Heterogeneity of the proliferative capacity of rat cholangiocytes after bile duct ligation. Am J Physiol: 1998; 274 4 Pt 1 G767 G775
31. Tietz P. S., Alpini G., Pham L. D., Larusso N. F. Somatostatin inhibits secretin-induced ductal hypercholeresis and exocytosis by cholangiocytes. Am J Physiol: 1995; 269 1 Pt 1 G110 G118
32. Caligiuri A., Glaser S., Rodgers R. E., et al. Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes. Am J Physiol: 1998; 275 4 Pt 1 G835 G846
33. Glaser S. S., Rodgers R. E., Phinizy J. L., et al. Gastrin inhibits secretin-induced ductal secretion by interaction with specific receptors on rat cholangiocytes. Am J Physiol: 1997; 273 5 Pt 1 G1061 G1070
34. Glaser S., Benedetti A., Marucci L., et al. Gastrin inhibits cholangiocyte growth in bile duct-ligated rats by interaction with cholecystokinin-B/Gastrin receptors via D-myo-inositol 1,4,5-triphosphate-, Ca(2+)-, and protein kinase C alpha-dependent mechanisms. Hepatology: 2000; 32 1 17 25
35. Glaser S., Alvaro D., Roskams T., et al. Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-gamma expression and decrease of PKA activity. Am J Physiol Gastrointest Liver Physiol: 2003; 284 4 G683 G694
36. Alvaro D., Alpini G., Jezequel A. M., et al. Role and mechanisms of action of acetylcholine in the regulation of rat cholangiocyte secretory functions. J Clin Invest: 1997; 100 6 1349 1362
37. Han Y., Glaser S., Meng F., et al. Recent advances in the morphological and functional heterogeneity of the biliary epithelium. Exp Biol Med (Maywood): 2013; 238 5 549 565
38. Strazzabosco M., Fiorotto R., Melero S., et al. Differentially expressed adenylyl cyclase isoforms mediate secretory functions in cholangiocyte subpopulation. Hepatology: 2009; 50 1 244 252
39. Chari R. S., Schutz S. M., Haebig J. E., et al. Adenosine nucleotides in bile. Am J Physiol: 1996; 270 2 Pt 1 G246 G252
40. Woo K., Sathe M., Kresge C., et al. Adenosine triphosphate release and purinergic (P2) receptor-mediated secretion in small and large mouse cholangiocytes. Hepatology: 2010; 52 5 1819 1828
41. Dutta A. K., Khimji A. K., Kresge C., et al. Identification and functional characterization of TMEM16A, a Ca2+-activated Cl- channel activated by extracellular nucleotides, in biliary epithelium. J Biol Chem: 2011; 286 1 766 776
42. Dutta A. K., Woo K., Khimji A. K., Kresge C., Feranchak A. P. Mechanosensitive Cl- secretion in biliary epithelium mediated through TMEM16A. Am J Physiol Gastrointest Liver Physiol: 2013; 304 1 G87 G98
43. Cardinale V., Wang Y., Carpino G., et al. The biliary tree-a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol: 2012; 9 4 231 240
44. Alpini G., Ulrich C., Roberts S., et al. Molecular and functional heterogeneity of cholangiocytes from rat liver after bile duct ligation. Am J Physiol: 1997; 272 2 Pt 1 G289 G297
45. Alvaro D., Alpini G., Onori P., et al. Estrogens stimulate proliferation of intrahepatic biliary epithelium in rats. Gastroenterology: 2000; 119 6 1681 1691
46. Alvaro D., Alpini G., Onori P., et al. Effect of ovariectomy on the proliferative capacity of intrahepatic rat cholangiocytes. Gastroenterology: 2002; 123 1 336 344
47. Marzioni M., Glaser S., Francis H., et al. Autocrine/paracrine regulation of the growth of the biliary tree by the neuroendocrine hormone serotonin. Gastroenterology: 2005; 128 1 121 137
48. LeSagE G., Alvaro D., Benedetti A., et al. Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats. Gastroenterology: 1999; 117 1 191 199
49. Gaudio E., Barbaro B., Alvaro D., et al. Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism. Gastroenterology: 2006; 130 4 1270 1282
50. Gaudio E., Onori P., Pannarale L., Alvaro D. Hepatic microcirculation and peribiliary plexus in experimental biliary cirrhosis: a morphological study. Gastroenterology: 1996; 111 4 1118 1124
51. Alvaro D., Mancino M. G., Glaser S., et al. Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver. Gastroenterology: 2007; 132 1 415 431
52. LeSage G. D., Glaser S. S., Marucci L., et al. Acute carbon tetrachloride feeding induces damage of large but not small cholangiocytes from BDL rat liver. Am J Physiol: 1999; 276 5 Pt 1 G1289 G1301
53. LeSage G. D., Benedetti A., Glaser S., et al. Acute carbon tetrachloride feeding selectively damages large, but not small, cholangiocytes from normal rat liver. Hepatology: 1999; 29 2 307 319
54. Alpini G., Glaser S. S., Ueno Y., et al. Bile acid feeding induces cholangiocyte proliferation and secretion: evidence for bile acid-regulated ductal secretion. Gastroenterology: 1999; 116 1 179 186
55. Alpini G., Ueno Y., Glaser S. S., et al. Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes. Hepatology: 2001; 34 5 868 876
56. Lesage G., Glaser S., Ueno Y., et al. Regression of cholangiocyte proliferation after cessation of ANIT feeding is coupled with increased apoptosis. Am J Physiol Gastrointest Liver Physiol: 2001; 281 1 G182 G190
57. Francis H., Glaser S., Ueno Y., et al. cAMP stimulates the secretory and proliferative capacity of the rat intrahepatic biliary epithelium through changes in the PKA/Src/MEK/ERK1/2 pathway. J Hepatol: 2004; 41 4 528 537
58. Alpini G., Franchitto A., Demorrow S., et al. Activation of alpha(1) -adrenergic receptors stimulate the growth of small mouse cholangiocytes via calcium-dependent activation of nuclear factor of activated T cells 2 and specificity protein 1. Hepatology: 2011; 53 2 628 639
59. Francis H. L., Demorrow S., Franchitto A., et al. Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms. Lab Invest: 2012; 92 2 282 294
60. Mancinelli R., Franchitto A., Glaser S., et al. GABA induces the differentiation of small into large cholangiocytes by activation of Ca(2+) /CaMK I-dependent adenylyl cyclase 8. Hepatology: 2013; 58 1 251 263
61. Liu Y., Meyer C., Xu C., et al. Animal models of chronic liver diseases. Am J Physiol Gastrointest Liver Physiol: 2013; 304 5 G449 G468
62. Kountouras J., Billing B. H., Scheuer P. J. Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat. Br J Exp Pathol: 1984; 65 3 305 311
63. Starkel P., Leclercq I. A. Animal models for the study of hepatic fibrosis. Best Pract Res Clin Gastroenterol: 2011; 25 2 319 333
64. Goldfarb S., Singer E. J., Popper H. Experimental cholangitis due to alpha-naphthyl-isothiocyanate (ANIT). Am J Pathol: 1962; 40 685 698
65. Ohta Y., Kongo M., Sasaki E., Harada N. Change in hepatic antioxidant defense system with liver injury development in rats with a single alpha-naphthylisothiocyanate intoxication. Toxicology: 1999; 139 3 265 275
66. Kodali P., Wu P., Lahiji P. A., Brown E. J., Maher J. J. ANIT toxicity toward mouse hepatocytes in vivo is mediated primarily by neutrophils via CD18. Am J Physiol Gastrointest Liver Physiol: 2006; 291 2 G355 G363
67. Chang M. L., Yeh C. T., Chang P. Y., Chen J. C. Comparison of murine cirrhosis models induced by hepatotoxin administration and common bile duct ligation. World J Gastroenterol: 2005; 11 27 4167 4172
68. Fickert P., Stöger U., Fuchsbichler A., et al. A new xenobiotic-induced mouse model of sclerosing cholangitis and biliary fibrosis. Am J Pathol: 2007; 171 2 525 536
69. Kakis G., Yousef I. M. Pathogenesis of lithocholate- and taurolithocholate-induced intrahepatic cholestasis in rats. Gastroenterology: 1978; 75 4 595 607
70. Beuers U., Denk G. U., Soroka C. J., et al. Taurolithocholic acid exerts cholestatic effects via phosphatidylinositol 3-kinase-dependent mechanisms in perfused rat livers and rat hepatocyte couplets. J Biol Chem: 2003; 278 20 17810 17818
71. Fickert P., Fuchsbichler A., Marschall H. U., et al. Lithocholic acid feeding induces segmental bile duct obstruction and destructive cholangitis in mice. Am J Pathol: 2006; 168 2 410 422
72. Trauner M., Fickert P., Halilbasic E., Moustafa T. Lessons from the toxic bile concept for the pathogenesis and treatment of cholestatic liver diseases. Wien Med Wochenschr: 2008; 158 19-20 542 548
73. Koarada S., Wu Y., Fertig N., et al. Genetic control of autoimmunity: protection from diabetes, but spontaneous autoimmune biliary disease in a nonobese diabetic congenic strain. J Immunol: 2004; 173 4 2315 2323
74. Irie J., Wu Y., Wicker L. S., 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
75. Moritoki Y., Tsuda M., Tsuneyama K., et al. B cells promote hepatic inflammation, biliary cyst formation, and salivary gland inflammation in the NOD.c3c4 model of autoimmune cholangitis. Cell Immunol: 2011; 268 1 16 23
76. Oertelt S., Lian Z. X., Cheng C. M., et al. Anti-mitochondrial antibodies and primary biliary cirrhosis in TGF-beta receptor II dominant-negative mice. J Immunol: 2006; 177 3 1655 1660
77. Li M. O., Wan Y. Y., Sanjabi S., Robertson A. K., Flavell R. A. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol: 2006; 24 99 146
78. Gorelik L., Flavell R. A. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity: 2000; 12 2 171 181
79. Ueno Y., Ambrosini Y. M., Moritoki Y., Ridgway W. M., Gershwin M. E. Murine models of autoimmune cholangitis. Curr Opin Gastroenterol: 2010; 26 3 274 279
80. Yang G. X., Lian Z. X., Chuang Y. H., et al. Adoptive transfer of CD8(+) T cells from transforming growth factor beta receptor type II (dominant negative form) induces autoimmune cholangitis in mice. Hepatology: 2008; 47 6 1974 1982
81. Marie J. C., Letterio J. J., Gavin M., Rudensky A. Y. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med: 2005; 201 7 1061 1067
82. Lan R. Y., Selmi C., Gershwin M. E. The regulatory, inflammatory, and T cell programming roles of interleukin-2 (IL-2). J Autoimmun: 2008; 31 1 7 12
83. Lan R. Y., Cheng C., Lian Z. X., et al. Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology: 2006; 43 4 729 737
84. Wakabayashi K., Lian Z. X., Moritoki Y., et al. IL-2 receptor alpha(-/-) mice and the development of primary biliary cirrhosis. Hepatology: 2006; 44 5 1240 1249
85. Willerford D. M., Chen J., Ferry J. A., Davidson L., Ma A., Alt F. W. Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment. Immunity: 1995; 3 4 521 530
86. 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
87. Prieto J., Qian C., García N., Díez J., Medina J. F. Abnormal expression of anion exchanger genes in primary biliary cirrhosis. Gastroenterology: 1993; 105 2 572 578
88. Salas J. T., Banales J. M., Sarvide S., et al. Ae2a,b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis. Gastroenterology: 2008; 134 5 1482 1493
89. Surh C. D., Coppel R., Gershwin M. E. Structural requirement for autoreactivity on human pyruvate dehydrogenase-E2, the major autoantigen of primary biliary cirrhosis. Implication for a conformational autoepitope. J Immunol: 1990; 144 9 3367 3374
90. Leung P. S., 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
91. Leung P. S., 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
92. Amano K., Leung P. S., 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
93. Wakabayashi K., Lian Z. X., Leung P. S., 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
94. Brown W. R., Kloppel T. M. The liver and IgA: immunological, cell biological and clinical implications. Hepatology: 1989; 9 5 763 784
95. 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
96. Ballardini G., Mirakian R., Bianchi F. B., Pisi E., Doniach D., Bottazzo G. F. Aberrant expression of HLA-DR antigens on bileduct epithelium in primary biliary cirrhosis: relevance to pathogenesis. Lancet: 1984; 2 8410 1009 1013
97. Saidman S. L., Duquesnoy R. J., Zeevi A., Fung J. J., Starzl T. E., Demetris A. J. Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes. Hepatology: 1991; 13 2 239 246
98. Ichiki Y., Selmi C., Shimoda S., Ishibashi H., Gordon S. C., Gershwin M. E. Mitochondrial antigens as targets of cellular and humoral auto-immunity in primary biliary cirrhosis. Clin Rev Allergy Immunol: 2005; 28 2 83 91
99. Yokomori H., Oda M., Ogi M., et al. Expression of adhesion molecules on mature cholangiocytes in canal of Hering and bile ductules in wedge biopsy samples of primary biliary cirrhosis. World J Gastroenterol: 2005; 11 28 4382 4389
100. Fava G., Glaser S., Francis H., Alpini G. The immunophysiology of biliary epithelium. Semin Liver Dis: 2005; 25 3 251 264
101. Ayres R. C., Neuberger J. M., Shaw J., Joplin R., Adams D. H. Intercellular adhesion molecule-1 and MHC antigens on human intrahepatic bile duct cells: effect of pro-inflammatory cytokines. Gut: 1993; 34 9 1245 1249
102. Tsuneyama K., Harada K., Yasoshima M., Kaji K., Gershwin M. E., Nakanuma Y. Expression of co-stimulatory factor B7-2 on the intrahepatic bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis: an immunohistochemical study. J Pathol: 1998; 186 2 126 130
103. Takeda K., Kojima Y., Ikejima K., et al. Death receptor 5 mediated-apoptosis contributes to cholestatic liver disease. Proc Natl Acad Sci U S A: 2008; 105 31 10895 10900
104. Chen X. M., O'Hara S. P., Nelson J. B., et al. Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to Cryptosporidium parvum via activation of NF-kappaB. J Immunol: 2005; 175 11 7447 7456
105. Nakamura M., Funami K., Komori A., et al. Increased expression of Toll-like receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers. Hepatol Int: 2008; 2 2 222 230
106. Harada K., Isse K., Sato Y., Ozaki S., Nakanuma Y. Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by upregulation of IRAK-M. Liver Int: 2006; 26 8 935 942
107. Kobayashi K., Hernandez L. D., Galán J. E., Janeway C. A. Jr, Medzhitov R., Flavell R. A. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell: 2002; 110 2 191 202
108. Woof J. M., Mestecky J. Mucosal immunoglobulins. Immunol Rev: 2005; 206 64 82
109. Tomana M., Kulhavy R., Mestecky J. Receptor-mediated binding and uptake of immunoglobulin A by human liver. Gastroenterology: 1988; 94 3 762 770
110. 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
111. Harada K., Ohba K., Ozaki S., et al. Peptide antibiotic human beta-defensin-1 and -2 contribute to antimicrobial defense of the intrahepatic biliary tree. Hepatology: 2004; 40 4 925 932
112. Leon M. P., Kirby J. A., Gibbs P., Burt A. D., Bassendine M. F. Immunogenicity of biliary epithelial cells: study of the expression of B7 molecules. J Hepatol: 1995; 22 5 591 595
113. Morita M., Watanabe Y., Akaike T. Inflammatory cytokines up-regulate intercellular adhesion molecule-1 expression on primary cultured mouse hepatocytes and T-lymphocyte adhesion. Hepatology: 1994; 19 2 426 431
114. Leon M. P., Bassendine M. F., Wilson J. L., Ali S., Thick M., Kirby J. A. Immunogenicity of biliary epithelium: investigation of antigen presentation to CD4+ T cells. Hepatology: 1996; 24 3 561 567
115. Cruickshank S. M., Southgate J., Selby P. J., Trejdosiewicz L. K. Expression and cytokine regulation of immune recognition elements by normal human biliary epithelial and established liver cell lines in vitro. J Hepatol: 1998; 29 4 550 558
116. Oo Y. H., Adams D. H. The role of chemokines in the recruitment of lymphocytes to the liver. J Autoimmun: 2010; 34 1 45 54
117. Reynoso-Paz S., Coppel R. L., Mackay I. R., Bass N. M., Ansari A. A., Gershwin M. E. The immunobiology of bile and biliary epithelium. Hepatology: 1999; 30 2 351 357
118. Spirlì C., Nathanson M. H., Fiorotto R., et al. Proinflammatory cytokines inhibit secretion in rat bile duct epithelium. Gastroenterology: 2001; 121 1 156 169
119. Morland C. M., Fear J., McNab G., Joplin R., Adams D. H. Promotion of leukocyte transendothelial cell migration by chemokines derived from human biliary epithelial cells in vitro. Proc Assoc Am Physicians: 1997; 109 4 372 382
120. Harada K., Shimoda S., Sato Y., Isse K., Ikeda H., Nakanuma Y. Periductal interleukin-17 production in association with biliary innate immunity contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis. Clin Exp Immunol: 2009; 157 2 261 270
121. Lan R. Y., Salunga T. L., Tsuneyama K., et al. Hepatic IL-17 responses in human and murine primary biliary cirrhosis. J Autoimmun: 2009; 32 1 43 51
122. Ramaswamy M., Deng M., Siegel R. M. Harnessing programmed cell death as a therapeutic strategy in rheumatic diseases. Nat Rev Rheumatol: 2011; 7 3 152 160
123. Nagata S., Hanayama R., Kawane K. Autoimmunity and the clearance of dead cells. Cell: 2010; 140 5 619 630
124. Henson P. M. Dampening inflammation. Nat Immunol: 2005; 6 12 1179 1181
125. Huynh M. L., Fadok V. A., Henson P. M. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest: 2002; 109 1 41 50
126. Casciola-Rosen L. A., Anhalt G., Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med: 1994; 179 4 1317 1330
127. Shi Y., Evans J. E., Rock K. L. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature: 2003; 425 6957 516 521
128. Koga H., Sakisaka S., Ohishi M., Sata M., Tanikawa K. Nuclear DNA fragmentation and expression of Bcl-2 in primary biliary cirrhosis. Hepatology: 1997; 25 5 1077 1084
129. Harada K., Ozaki S., Gershwin M. E., Nakanuma Y. Enhanced apoptosis relates to bile duct loss in primary biliary cirrhosis. Hepatology: 1997; 26 6 1399 1405
130. Harada K., Kono N., Tsuneyama K., Nakanuma Y. Cell-kinetic study of proliferating bile ductules in various hepatobiliary diseases. Liver: 1998; 18 4 277 284
131. Harada K., Furubo S., Ozaki S., Hiramatsu K., Sudo Y., Nakanuma Y. Increased expression of WAF1 in intrahepatic bile ducts in primary biliary cirrhosis relates to apoptosis. J Hepatol: 2001; 34 4 500 506
132. Tinmouth J., Lee M., Wanless I. R., Tsui F. W., Inman R., Heathcote E. J. Apoptosis of biliary epithelial cells in primary biliary cirrhosis and primary sclerosing cholangitis. Liver: 2002; 22 3 228 234
133. Lleo A., Gershwin M. E., Mantovani A., Invernizzi P. Towards common denominators in primary biliary cirrhosis: the role of IL-12. J Hepatol: 2012; 56 3 731 733
134. Hu B., Allina J., Bai J., Kesar V., Odin J. A. Catalase and estradiol inhibit mitochondrial protein S-glutathionylation. Mol Cell Biochem: 2012; 367 1-2 51 58
135. Allina J., Hu B., Sullivan D. M., et al. T cell targeting and phagocytosis of apoptotic biliary epithelial cells in primary biliary cirrhosis. J Autoimmun: 2006; 27 4 232 241
136. Rong G., Zhong R., Lleo A., et al. Epithelial cell specificity and apotope recognition by serum autoantibodies in primary biliary cirrhosis. Hepatology: 2011; 54 1 196 203