The Role of Inflammation in Cholestatic Liver Injury

References

• Zollner G, Trauner M. Mechanisms of cholestasis. Clin Liver Dis. 2008;12(1):1–26, vii. doi:10.1016/j.cld.2007.11.010
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Bernstein D, Shiffman ML, et al. Diagnosis and management of primary biliary cholangitis. Am J Gastroenterol. 2019;114(1):48–63. doi:10.1038/s41395-018-0390-3
   PubMed Web of Science ®Google Scholar
• Jüngst C, Berg T, Cheng J, et al. Intrahepatic cholestasis in common chronic liver diseases. Eur J Clin Invest. 2013;43(10):1069–1083. doi:10.1111/eci.12128
   PubMed Web of Science ®Google Scholar
• You H, Ma X, Efe C, et al. APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis. Hepatol Int. 2022;16(1):1–23. doi:10.1007/s12072-021-10276-6
   PubMed Web of Science ®Google Scholar
• Zhuang Y, Ortega-Ribera M, Thevkar Nagesh P, et al. Bile acid-induced IRF3 phosphorylation mediates cell death, inflammatory responses and fibrosis in cholestasis-induced liver and kidney injury via regulation of ZBP1. Hepatology. 2023. doi:10.1097/HEP.0000000000000611
   Google Scholar
• Xiao J, Li Z, Song Y, et al. Molecular Pathogenesis of Intrahepatic Cholestasis of Pregnancy. Can J Gastroenterol Hepatol. 2021;2021:6679322. doi:10.1155/2021/6679322
   PubMed Web of Science ®Google Scholar
• Hassan S, Hertel P. Overview of progressive familial intrahepatic cholestasis. Clin Liver Dis. 2022;26(3):371–390. doi:10.1016/j.cld.2022.03.003
   PubMed Web of Science ®Google Scholar
• Zhang Y, Lu Y, Ji H, Li Y. Anti-inflammatory, anti-oxidative stress and novel therapeutic targets for cholestatic liver injury. Biosci Trends. 2019;13(1):23–31. doi:10.5582/bst.2018.01247
   PubMed Web of Science ®Google Scholar
• Guo RF, Ward PA. Mediators and regulation of neutrophil accumulation in inflammatory responses in lung: insights from the IgG immune complex model. Free Radic Biol Med. 2002;33(3):303–310. doi:10.1016/S0891-5849(02)00823-7
   PubMed Web of Science ®Google Scholar
• Dold S, Laschke MW, Zhau Y, et al. P-selectin glycoprotein ligand-1-mediated leukocyte recruitment regulates hepatocellular damage in acute obstructive cholestasis in mice. Inflamm Res. 2010;59(4):291–298. doi:10.1007/s00011-009-0099-2
   PubMed Web of Science ®Google Scholar
• Ho JS, Buchweitz JP, Roth RA, Ganey PE. Identification of factors from rat neutrophils responsible for cytotoxicity to isolated hepatocytes. J Leukoc Biol. 1996;59(5):716–724. doi:10.1002/jlb.59.5.716
   PubMed Web of Science ®Google Scholar
• Gujral JS, Hinson JA, Jaeschke H. Chlorotyrosine protein adducts are reliable biomarkers of neutrophil-induced cytotoxicity in vivo. Comp Hepatol. 2004;3(Suppl 1):S48. doi:10.1186/1476-5926-2-S1-S48
   PubMedGoogle Scholar
• Gujral JS, Farhood A, Bajt ML, Jaeschke H. Neutrophils aggravate acute liver injury during obstructive cholestasis in bile duct-ligated mice. Hepatology. 2003;38(2):355–363. doi:10.1053/jhep.2003.50341
   PubMed Web of Science ®Google Scholar
• Woolbright BL, Antoine DJ, Jenkins RE, Bajt ML, Park BK, Jaeschke H. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice. Toxicol Appl Pharmacol. 2013;273(3):524–531. doi:10.1016/j.taap.2013.09.023
   PubMed Web of Science ®Google Scholar
• Georgiev P, Jochum W, Heinrich S, et al. Characterization of time-related changes after experimental bile duct ligation. Br J Surg. 2008;95(5):646–656. doi:10.1002/bjs.6050
   PubMed Web of Science ®Google Scholar
• Silva J, Magenta M, Sisti G, Serventi L, Gaither K. Association between complete blood count components and intrahepatic cholestasis of pregnancy. Cureus. 2020;12(12):e12381. doi:10.7759/cureus.12381
   PubMed Web of Science ®Google Scholar
• Barreiro O, Yanez-Mo M, Serrador JM, et al. Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol. 2002;157(7):1233–1245. doi:10.1083/jcb.200112126
   PubMed Web of Science ®Google Scholar
• Carman CV, Jun CD, Salas A, Springer TA. Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1. J Immunol. 2003;171(11):6135–6144. doi:10.4049/jimmunol.171.11.6135
   PubMed Web of Science ®Google Scholar
• Yang M, Ramachandran A, Yan HM, et al. Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice. Toxicol Lett. 2014;224(2):186–195. doi:10.1016/j.toxlet.2013.10.030
   PubMed Web of Science ®Google Scholar
• Cai SY, Ouyang X, Chen Y, et al. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight. 2017;2(5):e90780. doi:10.1172/jci.insight.90780
   PubMed Web of Science ®Google Scholar
• De Fernandez MA, Clark A, Triger DR. Neutrophil phagocytic and bactericidal function in primary biliary cirrhosis and other chronic liver diseases. Clin Exp Immunol. 1987;67(3):655–661.
   PubMed Web of Science ®Google Scholar
• Roughneen PT, Drath DB, Kulkarni AD, Kumar SC, Andrassy RJ, Rowlands BJ. Inflammatory cell function in young rodents with experimental cholestasis: investigations of functional deficits, their etiology, and their reversibility. J Pediatr Surg. 1989;24(7):668–673. doi:10.1016/S0022-3468(89)80716-X
   PubMed Web of Science ®Google Scholar
• Levy R, Schlaeffer F, Keynan A, Nagauker O, Yaari A, Sikuler E. Increased neutrophil function induced by bile duct ligation in a rat model. Hepatology. 1993;17(5):908–914. doi:10.1002/hep.1840170522
   PubMed Web of Science ®Google Scholar
• Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol. 2014;60(5):1090–1096. doi:10.1016/j.jhep.2013.12.025
   PubMed Web of Science ®Google Scholar
• Jenne CN, Kubes P. Immune surveillance by the liver. Nat Immunol. 2013;14(10):996–1006. doi:10.1038/ni.2691
   PubMed Web of Science ®Google Scholar
• Zandieh A, Payabvash S, Pasalar P, et al. Gadolinium chloride, a Kupffer cell inhibitor, attenuates hepatic injury in a rat model of chronic cholestasis. Hum Exp Toxicol. 2011;30(11):1804–1810. doi:10.1177/0960327111400106
   PubMed Web of Science ®Google Scholar
• Kim SY, Jeong JM, Kim SJ, et al. Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex. Nat Commun. 2017;8(1):2247. doi:10.1038/s41467-017-02325-2
   PubMedGoogle Scholar
• Mulder J, Karpen SJ, Tietge UJ, Kuipers F. Nuclear receptors: mediators and modifiers of inflammation-induced cholestasis. Front Biosci. 2009;14(7):2599–2630. doi:10.2741/3400
   Google Scholar
• Lou G, Ma X, Fu X, et al. GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells. PLoS One. 2014;9(4):e93567. doi:10.1371/journal.pone.0093567
   PubMed Web of Science ®Google Scholar
• Fu HY, Bao WM, Yang CX, et al. Kupffer cells regulate natural killer cells via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) interaction and cytokines in a primary biliary cholangitis mouse model. Med Sci Monit. 2020;26:e923726. doi:10.12659/MSM.923726
   PubMed Web of Science ®Google Scholar
• Wang YD, Chen WD, Yu D, Forman BM, Huang W. The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor κ light-chain enhancer of activated B cells (NF-κB) in mice. Hepatology. 2011;54(4):1421–1432. doi:10.1002/hep.24525
   PubMed Web of Science ®Google Scholar
• Li WT, Luo QQ, Wang B, et al. Bile acids induce visceral hypersensitivity via mucosal mast cell-to-nociceptor signaling that involves the farnesoid X receptor/nerve growth factor/transient receptor potential vanilloid 1 axis. FASEB j. 2019;33(2):2435–2450. doi:10.1096/fj.201800935RR
   PubMed Web of Science ®Google Scholar
• Jones H, Hargrove L, Kennedy L, et al. Inhibition of mast cell-secreted histamine decreases biliary proliferation and fibrosis in primary sclerosing cholangitis Mdr2(-/-) mice. Hepatology. 2016;64(4):1202–1216. doi:10.1002/hep.28704
   PubMed Web of Science ®Google Scholar
• Taylor SA, Chen SY, Gadhvi G, et al. Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations. PLoS One. 2021;16(1):e0244743. doi:10.1371/journal.pone.0244743
   PubMed Web of Science ®Google Scholar
• Tian X, Wang Y, Lu Y, et al. Conditional depletion of macrophages ameliorates cholestatic liver injury and fibrosis via lncRNA-H19. Cell Death Dis. 2021;12(7):646. doi:10.1038/s41419-021-03931-1
   PubMed Web of Science ®Google Scholar
• Wang J, Xu Y, Chen Z, et al. Liver immune profiling reveals pathogenesis and therapeutics for biliary atresia. Cell. 2020;183(7):1867–1883.e1826. doi:10.1016/j.cell.2020.10.048
   PubMed Web of Science ®Google Scholar
• Metz M, Maurer M. Mast cells--key effector cells in immune responses. Trends Immunol. 2007;28(5):234–241. doi:10.1016/j.it.2007.03.003
   PubMed Web of Science ®Google Scholar
• Bischoff SC. Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol. 2007;7(2):93–104. doi:10.1038/nri2018
   PubMed Web of Science ®Google Scholar
• Jarido V, Kennedy L, Hargrove L, et al. The emerging role of mast cells in liver disease. Am J Physiol Gastrointest Liver Physiol. 2017;313(2):G89–G101. doi:10.1152/ajpgi.00333.2016
   PubMed Web of Science ®Google Scholar
• Grizzi F, Di Caro G, Laghi L, et al. Mast cells and the liver aging process. Immun Ageing. 2013;10(1):9. doi:10.1186/1742-4933-10-9
   PubMedGoogle Scholar
• Yamashiro M, Kouda W, Kono N, Tsuneyama K, Matsui O, Nakanuma Y. Distribution of intrahepatic mast cells in various hepatobiliary disorders. An immunohistochemical study. Virchows Arch. 1998;433(5):471–479. doi:10.1007/s004280050276
   PubMed Web of Science ®Google Scholar
• Huntzicker EG, Hötzel K, Choy L, et al. Differential effects of targeting Notch receptors in a mouse model of liver cancer. Hepatology. 2015;61(3):942–952. doi:10.1002/hep.27566
   PubMed Web of Science ®Google Scholar
• Yurdakul Ertan H, Özbakış Dengiz G, Barut F, et al. The Investigation of Therapeutic Implications of Mast Cell Stabilizer Cromolyn Sodium on Cholestasis and Cholestatic Pruritus in Experimental Cholestasis. Turk J Gastroenterol. 2023;34(1):62–72. doi:10.5152/tjg.2022.21744
   PubMed Web of Science ®Google Scholar
• Meadows V, Kennedy L, Ekser B, et al. Mast cells regulate ductular reaction and intestinal inflammation in cholestasis through farnesoid X receptor signaling. Hepatology. 2021;74(5):2684–2698. doi:10.1002/hep.32028
   PubMed Web of Science ®Google Scholar
• Meadows V, Kennedy L, Kundu D, Alpini G, Francis H. Bile acid receptor therapeutics effects on chronic liver diseases. Front Med. 2020;7:15. doi:10.3389/fmed.2020.00015
   Web of Science ®Google Scholar
• Gonzalez MI, Vannan DT, Eksteen B, Flores-Sotelo I, Reyes JL. Mast cells in immune-mediated cholangitis and cholangiocarcinoma. Cells. 2022;11(3):375. doi:10.3390/cells11030375
   PubMed Web of Science ®Google Scholar
• Aller M, Martínez V, Arias A, et al. Mast cell-mediated splanchnic cholestatic inflammation. Clin Res Hepatol Gastroenterol. 2019;43(5):561–574. doi:10.1016/j.clinre.2019.02.001
   PubMed Web of Science ®Google Scholar
• Komi DEA, Rambasek T, Wöhrl S. Mastocytosis: from a Molecular Point of View. Clin Rev Allergy Immunol. 2018;54(3):397–411. doi:10.1007/s12016-017-8619-2
   PubMed Web of Science ®Google Scholar
• Zhou K, Xie G, Wen J, et al. Histamine is correlated with liver fibrosis in biliary atresia. Dig Liver Dis. 2016;48(8):921–926. doi:10.1016/j.dld.2016.05.001
   PubMedGoogle Scholar
• Carotti S, Guarino MP, Cicala M, et al. Effect of ursodeoxycholic acid on inflammatory infiltrate in gallbladder muscle of cholesterol gallstone patients. Neurogastroenterol Motil. 2010;22(8):866–873, e232. doi:10.1111/j.1365-2982.2010.01510.x
   PubMed Web of Science ®Google Scholar
• Shimoda S, Ishikawa F, Kamihira T, et al. Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory. Gastroenterology. 2006;131(2):606–618. doi:10.1053/j.gastro.2006.05.056
   PubMed Web of Science ®Google Scholar
• Mack CL, Falta MT, Sullivan AK, et al. Oligoclonal expansions of CD4+ and CD8+ T-cells in the target organ of patients with biliary atresia. Gastroenterology. 2007;133(1):278–287. doi:10.1053/j.gastro.2007.04.032
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1084/jem.20010956
   PubMed Web of Science ®Google Scholar
• Glaser F, John C, Engel B, et al. Liver infiltrating T cells regulate bile acid metabolism in experimental cholangitis. J Hepatol. 2019;71(4):783–792. doi:10.1016/j.jhep.2019.05.030
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1002/hep.21123
   PubMed Web of Science ®Google Scholar
• Tucker RM, Feldman AG, Fenner EK, Mack CL. Regulatory T cells inhibit Th1 cell-mediated bile duct injury in murine biliary atresia. J Hepatol. 2013;59(4):790–796. doi:10.1016/j.jhep.2013.05.010
   PubMed Web of Science ®Google Scholar
• Barrat FJ, Cua DJ, Boonstra A, et al. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med. 2002;195(5):603–616. doi:10.1084/jem.20011629
   PubMed Web of Science ®Google Scholar
• Akkaya M, Kwak K, Pierce SK. B cell memory: building two walls of protection against pathogens. Nat Rev Immunol. 2020;20(4):229–238. doi:10.1038/s41577-019-0244-2
   PubMed Web of Science ®Google Scholar
• Cyster JG, Allen CDC. B cell responses: cell interaction dynamics and decisions. Cell. 2019;177(3):524–540. doi:10.1016/j.cell.2019.03.016
   PubMed Web of Science ®Google Scholar
• Migita K, Ilyassova B, Kovzel EF, et al. Serum BAFF and April levels in patients with PBC. Clin Immunol. 2010;134(2):217–225. doi:10.1016/j.clim.2009.09.007
   PubMed Web of Science ®Google Scholar
• Jin Q, Moritoki Y, Lleo A, et al. Comparative analysis of portal cell infiltrates in antimitochondrial autoantibody-positive versus antimitochondrial autoantibody-negative primary biliary cirrhosis. Hepatology. 2012;55(5):1495–1506. doi:10.1002/hep.25511
   PubMed Web of Science ®Google Scholar
• Li Y, Wang W, Tang L, et al. Chemokine (C-X-C motif) ligand 13 promotes intrahepatic chemokine (C-X-C motif) receptor 5+ lymphocyte homing and aberrant B-cell immune responses in primary biliary cirrhosis. Hepatology. 2015;61(6):1998–2007. doi:10.1002/hep.27725
   PubMed Web of Science ®Google Scholar
• Bednarek J, Traxinger B, Brigham D, et al. Cytokine-producing B cells promote immune-mediated bile duct injury in murine biliary atresia. Hepatology. 2018;68(5):1890–1904. doi:10.1002/hep.30051
   PubMed Web of Science ®Google Scholar
• Zhang B, Hu M, Zhang P, et al. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis. Braz J Med Biol Res. 2013;46(5):433–439.
   PubMed Web of Science ®Google Scholar
• Takahashi T, Miura T, Nakamura J, et al. Plasma cells and the chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis. Hepatology. 2012;55(3):846–855.
   PubMed Web of Science ®Google Scholar
• Dhirapong A, Lleo A, Yang GX, et al. B cell depletion therapy exacerbates murine primary biliary cirrhosis. Hepatology. 2011;53(2):527–535. doi:10.1002/hep.24044
   PubMed Web of Science ®Google Scholar
• Bonorino P, Ramzan M, Camous X, et al. Fine characterization of intrahepatic NK cells expressing natural killer receptors in chronic hepatitis B and C. J Hepatol. 2009;51(3):458–467. doi:10.1016/j.jhep.2009.05.030
   PubMed Web of Science ®Google Scholar
• Wu Y, Kuang DM, Pan WD, et al. Monocyte/macrophage-elicited natural killer cell dysfunction in hepatocellular carcinoma is mediated by CD48/2B4 interactions. Hepatology. 2013;57(3):1107–1116. doi:10.1002/hep.26192
   PubMed Web of Science ®Google Scholar
• Wehr A, Baeck C, Ulmer F, et al. Pharmacological inhibition of the chemokine CXCL16 diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. PLoS One. 2014;9(11):e112327. doi:10.1371/journal.pone.0112327
   PubMed Web of Science ®Google Scholar
• Grégoire C, Chasson L, Luci C, et al. The trafficking of natural killer cells. Immunol Rev. 2007;220(1):169–182. doi:10.1111/j.1600-065X.2007.00563.x
   PubMedGoogle Scholar
• Rattay S, Graf D, Kislat A, et al. Anti-inflammatory consequences of bile acid accumulation in virus-infected bile duct ligated mice. PLoS One. 2018;13(6):e0199863. doi:10.1371/journal.pone.0199863
   PubMed Web of Science ®Google Scholar
• Guo C, Zhu J, Pu CL, Deng YH, Zhang MM. Combinatory effects of hepatic CD8+ and NK lymphocytes in bile duct injury from biliary atresia. Pediatr Res. 2012;71(6):638–644. doi:10.1038/pr.2012.17
   PubMed Web of Science ®Google Scholar
• van Dommelen SL, Sumaria N, Schreiber RD, Scalzo AA, Smyth MJ, Degli-Esposti MA. Perforin and granzymes have distinct roles in defensive immunity and immunopathology. Immunity. 2006;25(5):835–848. doi:10.1016/j.immuni.2006.09.010
   PubMed Web of Science ®Google Scholar
• Qian C, Jiang T, Zhang W, et al. Increased IL-23 and IL-17 expression by peripheral blood cells of patients with primary biliary cirrhosis. Cytokine. 2013;64(1):172–180. doi:10.1016/j.cyto.2013.07.005
   PubMed Web of Science ®Google Scholar
• Shimoda S, Harada K, Niiro H, et al. Interaction between Toll-like receptors and natural killer cells in the destruction of bile ducts in primary biliary cirrhosis. Hepatology. 2011;53(4):1270–1281. doi:10.1002/hep.24194
   PubMed Web of Science ®Google Scholar
• Chuang YH, Lian ZX, Tsuneyama K, et al. Increased killing activity and decreased cytokine production in NK cells in patients with primary biliary cirrhosis. J Autoimmun. 2006;26(4):232–240. doi:10.1016/j.jaut.2006.04.001
   PubMed Web of Science ®Google Scholar
• Zhao ZB, Lu FT, Ma HD, et al. Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4(+) T cells. Cell Mol Immunol. 2020;17(2):178–189. doi:10.1038/s41423-019-0199-z
   PubMed Web of Science ®Google Scholar
• Boes M, Prodeus AP, Schmidt T, Carroll MC, Chen J. A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection. J Exp Med. 1998;188(12):2381–2386. doi:10.1084/jem.188.12.2381
   PubMed Web of Science ®Google Scholar
• Lleo A, Liao J, Invernizzi P, et al. Immunoglobulin M levels inversely correlate with CD40 ligand promoter methylation in patients with primary biliary cirrhosis. Hepatology. 2012;55(1):153–160. doi:10.1002/hep.24630
   PubMed Web of Science ®Google Scholar
• Lian C, Zhao Y, Sun J, Zhao L, Zhang F. Role of cell autophagy in the generation of IgM and hepatic fibrosis in primary biliary cholangitis. Clin Rheumatol. 2020;39(11):3499–3506. doi:10.1007/s10067-020-05111-6
   PubMed Web of Science ®Google Scholar
• Luo Y, Brigham D, Bednarek J, et al. Unique cholangiocyte-targeted IgM autoantibodies correlate with poor outcome in biliary atresia. Hepatology. 2021;73(5):1855–1867. doi:10.1002/hep.31504
   PubMed Web of Science ®Google Scholar
• Marshall K, Jin J, Atkinson C, et al. Natural immunoglobulin M initiates an inflammatory response important for both hepatic ischemia reperfusion injury and regeneration in mice. Hepatology. 2018;67(2):721–735. doi:10.1002/hep.29512
   PubMed Web of Science ®Google Scholar
• Abe K, Takahashi A, Nozawa Y, et al. The utility of IgG, IgM, and CD138 immunohistochemistry in the evaluation of autoimmune liver diseases. Med Mol Morphol. 2014;47(3):162–168. doi:10.1007/s00795-014-0082-z
   PubMed Web of Science ®Google Scholar
• Surh CD, Cooper AE, Coppel RL, et al. The predominance of IgG3 and IgM isotype antimitochondrial autoantibodies against recombinant fused mitochondrial polypeptide in patients with primary biliary cirrhosis. Hepatology. 1988;8(2):290–295. doi:10.1002/hep.1840080217
   PubMed Web of Science ®Google Scholar
• Pang SY, Dai YM, Zhang RZ, et al. Autoimmune liver disease-related autoantibodies in patients with biliary atresia. World J Gastroenterol. 2018;24(3):387–396. doi:10.3748/wjg.v24.i3.387
   PubMed Web of Science ®Google Scholar
• Lu BR, Brindley SM, Tucker RM, Lambert CL, Mack CL. α-enolase autoantibodies cross-reactive to viral proteins in a mouse model of biliary atresia. Gastroenterology. 2010;139(5):1753–1761. doi:10.1053/j.gastro.2010.07.042
   PubMed Web of Science ®Google Scholar
• Terrier B, Degand N, Guilpain P, Servettaz A, Guillevin L, Mouthon L. Alpha-enolase: a target of antibodies in infectious and autoimmune diseases. Autoimmun Rev. 2007;6(3):176–182. doi:10.1016/j.autrev.2006.10.004
   PubMed Web of Science ®Google Scholar
• Gao X, Ma H, Niu J, Li D. FcγRIIB expression increases during primary biliary cholangitis. Mol Immunol. 2023;162:30–37. doi:10.1016/j.molimm.2023.08.001
   PubMed Web of Science ®Google Scholar
• Tanaka A, Nezu S, Uegaki S, et al. The clinical significance of IgA antimitochondrial antibodies in sera and saliva in primary biliary cirrhosis. Ann N Y Acad Sci. 2007;1107:259–270. doi:10.1196/annals.1381.028
   PubMed Web of Science ®Google Scholar
• Tanaka A, Nalbandian G, Leung PS, et al. Mucosal immunity and primary biliary cirrhosis: presence of antimitochondrial antibodies in urine. Hepatology. 2000;32(5):910–915. doi:10.1053/jhep.2000.19254
   PubMed Web of Science ®Google Scholar
• Emancipator SN, Gallo GR, Razaboni R, Lamm ME. Experimental cholestasis promotes the deposition of glomerular IgA immune complexes. Am J Pathol. 1983;113(1):19–26.
   PubMed Web of Science ®Google Scholar
• Geha RS, Jabara HH, Brodeur SR. The regulation of immunoglobulin E class-switch recombination. Nat Rev Immunol. 2003;3(9):721–732. doi:10.1038/nri1181
   PubMed Web of Science ®Google Scholar
• Tabibian JH, Enders F, Imam MH, Kolar G, Lindor KD, Talwalkar JA. Association between serum IgE level and adverse clinical endpoints in primary sclerosing cholangitis. Ann Hepatol. 2014;13(3):384–389. doi:10.1016/S1665-2681(19)30869-5
   PubMed Web of Science ®Google Scholar
• Shimomura I, Takase Y, Matsumoto S, et al. Primary sclerosing cholangitis associated with increased peripheral eosinophils and serum IgE. J Gastroenterol. 1996;31(5):737–741. doi:10.1007/BF02347627
   PubMed Web of Science ®Google Scholar
• Shen DZ. A target role for mast cell in the prevention and therapy of hepatic fibrosis. Med Hypotheses. 2008;70(4):760–764. doi:10.1016/j.mehy.2007.07.042
   PubMed Web of Science ®Google Scholar
• Heine G, Dahten A, Hilt K, et al. Liver X receptors control IgE expression in B cells. J Immunol. 2009;182(9):5276–5282. doi:10.4049/jimmunol.0801804
   PubMed Web of Science ®Google Scholar
• Geier A, Dietrich CG, Voigt S, et al. Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis. Hepatology. 2003;38(2):345–354. doi:10.1053/jhep.2003.50317
   PubMed Web of Science ®Google Scholar
• Hartmann G, Cheung AK, Piquette-Miller M. Inflammatory cytokines, but not bile acids, regulate expression of murine hepatic anion transporters in endotoxemia. J Pharmacol Exp Ther. 2002;303(1):273–281. doi:10.1124/jpet.102.039404
   PubMed Web of Science ®Google Scholar
• Sharanek A, Burban A, Ciriaci N, Guillouzo A. Pro-inflammatory cytokines enhance dilatation of bile canaliculi caused by cholestatic antibiotics. Toxicol In Vitro. 2019;58:51–59. doi:10.1016/j.tiv.2019.03.015
   PubMed Web of Science ®Google Scholar
• Bruccoleri A, Gallucci R, Germolec DR, et al. Induction of early-immediate genes by tumor necrosis factor alpha contribute to liver repair following chemical-induced hepatotoxicity. Hepatology. 1997;25(1):133–141. doi:10.1002/hep.510250125
   PubMed Web of Science ®Google Scholar
• Siewert E, Dietrich CG, Lammert F, et al. Interleukin-6 regulates hepatic transporters during acute-phase response. Biochem Biophys Res Commun. 2004;322(1):232–238. doi:10.1016/j.bbrc.2004.07.102
   PubMed Web of Science ®Google Scholar
• Liu G, Wang X, Yang T, et al. High interleukin-8 levels associated with decreased survival in patients with cirrhosis following transjugular intrahepatic portosystemic shunt. Front Med. 2022;9:829245. doi:10.3389/fmed.2022.829245
   Web of Science ®Google Scholar
• Neuman M, Angulo P, Malkiewicz I, et al. Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary cirrhosis. J Gastroenterol Hepatol. 2002;17(2):196–202. doi:10.1046/j.1440-1746.2002.02672.x
   PubMed Web of Science ®Google Scholar
• Yang CY, Ma X, Tsuneyama K, et al. IL-12/Th1 and IL-23/Th17 biliary microenvironment in primary biliary cirrhosis: implications for therapy. Hepatology. 2014;59(5):1944–1953. doi:10.1002/hep.26979
   PubMed Web of Science ®Google Scholar
• Spirlì C, Nathanson MH, Fiorotto R, et al. Proinflammatory cytokines inhibit secretion in rat bile duct epithelium. Gastroenterology. 2001;121(1):156–169. doi:10.1053/gast.2001.25516
   PubMed Web of Science ®Google Scholar
• Knolle P, Schlaak J, Uhrig A, Kempf P, Meyer Zum Büschenfelde KH, Gerken G. Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. J Hepatol. 1995;22(2):226–229. doi:10.1016/0168-8278(95)80433-1
   PubMed Web of Science ®Google Scholar
• Milner JD, Orekov T, Ward JM, et al. Sustained IL-4 exposure leads to a novel pathway for hemophagocytosis, inflammation, and tissue macrophage accumulation. Blood. 2010;116(14):2476–2483. doi:10.1182/blood-2009-11-255174
   PubMed Web of Science ®Google Scholar
• Nagano T, Yamamoto K, Matsumoto S, et al. Cytokine profile in the liver of primary biliary cirrhosis. J Clin Immunol. 1999;19(6):422–427. doi:10.1023/A:1020511002025
   PubMed Web of Science ®Google Scholar
• Bedke T, Muscate F, Soukou S, Gagliani N, Huber S. Title: IL-10-producing T cells and their dual functions. Semin Immunol. 2019;44:101335. doi:10.1016/j.smim.2019.101335
   PubMed Web of Science ®Google Scholar
• Lin Z, Tian Y, Chai C, et al. The association of immune-related genes and the potential role of IL10 with biliary atresia. Pediatr Res. 2023. doi:10.1038/s41390-023-02626-x
   Web of Science ®Google Scholar
• Huang S, Liu Y, Guo N, Liu X, Li G, Du Q. Serum profiles of inflammatory cytokines associated with intrahepatic cholestasis of pregnancy. J Matern Fetal Neonatal Med. 2022;35(25):10072–10081. doi:10.1080/14767058.2022.2089551
   PubMed Web of Science ®Google Scholar
• Sasaki M, Miyakoshi M, Sato Y, Nakanuma Y. Modulation of the microenvironment by senescent biliary epithelial cells may be involved in the pathogenesis of primary biliary cirrhosis. J Hepatol. 2010;53(2):318–325. doi:10.1016/j.jhep.2010.03.008
   PubMed Web of Science ®Google Scholar
• Isse K, Harada K, Zen Y, et al. Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts. Hepatology. 2005;41(3):506–516. doi:10.1002/hep.20582
   PubMed Web of Science ®Google Scholar
• Limongi F. Th1 cytokines and chemokines in primary biliary cirrhosis. Clin Ter. 2015;166(2):e122–e125. doi:10.7417/CT.2015.1834
   PubMedGoogle Scholar
• Lin F, Shi H, Liu D, et al. Association of CCL11, CCL24 and CCL26 with primary biliary cholangitis. Int Immunopharmacol. 2019;67:372–377. doi:10.1016/j.intimp.2018.12.026
   PubMed Web of Science ®Google Scholar
• Konishi T, Schuster RM, Goetzman HS, Caldwell CC, Lentsch AB. Cell-specific regulatory effects of CXCR2 on cholestatic liver injury. Am J Physiol Gastrointest Liver Physiol. 2019;317(6):G773–G783. doi:10.1152/ajpgi.00080.2019
   PubMed Web of Science ®Google Scholar
• Köhl J. The role of complement in danger sensing and transmission. Immunol Res. 2006;34(2):157–176. doi:10.1385/IR:34:2:157
   PubMed Web of Science ®Google Scholar
• Bengtson A, Heideman M. Anaphylatoxin formation in sepsis. Arch Surg. 1988;123(5):645–649. doi:10.1001/archsurg.1988.01400290131023
   PubMedGoogle Scholar
• Sjöberg AP, Trouw LA, Blom AM. Complement activation and inhibition: a delicate balance. Trends Immunol. 2009;30(2):83–90. doi:10.1016/j.it.2008.11.003
   PubMed Web of Science ®Google Scholar
• Lin CJ, Hu ZG, Yuan GD, Lei B, He SQ. Complements are involved in alcoholic fatty liver disease, hepatitis and fibrosis. World J Hepatol. 2018;10(10):662–669. doi:10.4254/wjh.v10.i10.662
   PubMed Web of Science ®Google Scholar
• Liang J, Li H, Fu J, et al. A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants. Gastroenterol Hepatol. 2022;45(1):47–58. doi:10.1016/j.gastrohep.2021.02.020
   PubMed Web of Science ®Google Scholar
• Guo Z, Chen J, Zeng Y, et al. Complement inhibition alleviates cholestatic liver injury through mediating macrophage infiltration and function in mice. Front Immunol. 2021;12:785287. doi:10.3389/fimmu.2021.785287
   PubMed Web of Science ®Google Scholar
• Li J, Pircher PC, Schulman IG, Westin SK. Regulation of complement C3 expression by the bile acid receptor FXR. J Biol Chem. 2005;280(9):7427–7434. doi:10.1074/jbc.M411473200
   PubMed Web of Science ®Google Scholar
• Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10(2):417–426. doi:10.1016/S1097-2765(02)00599-3
   PubMed Web of Science ®Google Scholar
• Wan X, Xu C, Yu C, Li Y. Role of NLRP3 Inflammasome in the Progression of NAFLD to NASH. Can J Gastroenterol Hepatol. 2016;2016:6489012. doi:10.1155/2016/6489012
   PubMed Web of Science ®Google Scholar
• Wu Y, Qiu G, Zhang H, et al. Dexmedetomidine alleviates hepatic ischaemia-reperfusion injury via the PI3K/AKT/Nrf2-NLRP3 pathway. J Cell Mol Med. 2021;25(21):9983–9994. doi:10.1111/jcmm.16871
   PubMed Web of Science ®Google Scholar
• Matsushita H, Miyake Y, Takaki A, et al. TLR4, TLR9, and NLRP3 in biliary epithelial cells of primary sclerosing cholangitis: relationship with clinical characteristics. J Gastroenterol Hepatol. 2015;30(3):600–608. doi:10.1111/jgh.12711
   PubMed Web of Science ®Google Scholar
• Tian J, Yang G, Chen HY, et al. Galectin-3 regulates inflammasome activation in cholestatic liver injury. FASEB j. 2016;30(12):4202–4213. doi:10.1096/fj.201600392RR
   PubMed Web of Science ®Google Scholar
• Gaul S, Leszczynska A, Alegre F, et al. Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis. J Hepatol. 2021;74(1):156–167. doi:10.1016/j.jhep.2020.07.041
   PubMed Web of Science ®Google Scholar
• Frissen M, Liao L, Schneider KM, et al. Bidirectional role of NLRP3 during acute and chronic cholestatic liver injury. Hepatology. 2021;73(5):1836–1854. doi:10.1002/hep.31494
   PubMed Web of Science ®Google Scholar
• Hao H, Cao L, Jiang C, et al. Farnesoid X receptor regulation of the NLRP3 inflammasome underlies cholestasis-associated sepsis. Cell Metab. 2017;25(4):856–867.e855. doi:10.1016/j.cmet.2017.03.007
   PubMed Web of Science ®Google Scholar
• Balazs I, Horvath A, Leber B, et al. Serum bile acids in liver cirrhosis promote neutrophil dysfunction. Clin Transl Med. 2022;12(2):e735. doi:10.1002/ctm2.735
   PubMed Web of Science ®Google Scholar
• Cariello M, Piccinin E, Garcia-Irigoyen O, Sabbà C, Moschetta A. Nuclear receptor FXR, bile acids and liver damage: introducing the progressive familial intrahepatic cholestasis with FXR mutations. Biochim Biophys Acta Mol Basis Dis. 2018;1864(4 Pt B):1308–1318. doi:10.1016/j.bbadis.2017.09.019
   PubMed Web of Science ®Google Scholar
• Allen K, Kim ND, Moon JO, Copple BL. Upregulation of early growth response factor-1 by bile acids requires mitogen-activated protein kinase signaling. Toxicol Appl Pharmacol. 2010;243(1):63–67. doi:10.1016/j.taap.2009.11.013
   PubMed Web of Science ®Google Scholar
• Chen W, Ding M, Ji L, et al. Bile acids promote the development of HCC by activating inflammasome. Hepatol Commun. 2023;7(9). doi:10.1097/HC9.0000000000000217
   Web of Science ®Google Scholar
• Yamada K, Lim BO, Sugano M. Suppression of immunoglobulin production of rat lymphocytes by bile acids. Vitro Cell Dev Biol Anim. 1993;29(11):840–841. doi:10.1007/BF02631360
   Google Scholar
• Keane RM, Gadacz TR, Munster AM, Birmingham W, Winchurch RA. Impairment of human lymphocyte function by bile salts. Surgery. 1984;95(4):439–443.
   PubMed Web of Science ®Google Scholar
• Sung JJ, Go MY. Reversible Kupffer cell suppression in biliary obstruction is caused by hydrophobic bile acids. J Hepatol. 1999;30(3):413–418. doi:10.1002/hep.24757
   PubMed Web of Science ®Google Scholar
• Strnad P, Tacke F, Koch A, Trautwein C. Liver - guardian, modifier and target of sepsis. Nat Rev Gastroenterol Hepatol. 2017;14(1):55–66. doi:10.1038/nrgastro.2016.168
   PubMed Web of Science ®Google Scholar
• Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60(6):1310–1324. doi:10.1016/j.jhep.2014.01.024
   PubMed Web of Science ®Google Scholar
• Recknagel P, Gonnert FA, Westermann M, et al. Liver dysfunction and phosphatidylinositol-3-kinase signalling in early sepsis: experimental studies in rodent models of peritonitis. PLoS Med. 2012;9(11):e1001338. doi:10.1371/journal.pmed.1001338
   PubMed Web of Science ®Google Scholar
• Bahador M, Cross AS. From therapy to experimental model: a hundred years of endotoxin administration to human subjects. J Endotoxin Res. 2007;13(5):251–279. doi:10.1177/0968051907085986
   PubMedGoogle Scholar
• Remetic J, Ghallab A, Hobloss Z, et al. Loss of bile salt export pump aggravates lipopolysaccharide-induced liver injury in mice due to impaired hepatic endotoxin clearance. Hepatology. 2022;75(5):1095–1109. doi:10.1002/hep.32289
   PubMed Web of Science ®Google Scholar
• Trussoni CE, Tabibian JH, Splinter PL, O’Hara SP. Lipopolysaccharide (LPS)-induced biliary epithelial cell nras activation requires Epidermal Growth Factor Receptor (EGFR). PLoS One. 2015;10(4):e0125793. doi:10.1371/journal.pone.0125793
   PubMed Web of Science ®Google Scholar
• Seki E, De Minicis S, Osterreicher CH, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 2007;13(11):1324–1332. doi:10.1038/nm1663
   PubMed Web of Science ®Google Scholar
• Horvatits T, Trauner M, Fuhrmann V. Hypoxic liver injury and cholestasis in critically ill patients. Curr Opin Crit Care. 2013;19(2):128–132. doi:10.1097/MCC.0b013e32835ec9e6
   PubMed Web of Science ®Google Scholar
• Koskinas J, Gomatos IP, Tiniakos DG, et al. Liver histology in ICU patients dying from sepsis: a clinico-pathological study. World J Gastroenterol. 2008;14(9):1389–1393. doi:10.3748/wjg.14.1389
   PubMed Web of Science ®Google Scholar
• Jenniskens M, Langouche L, Vanwijngaerden YM, Mesotten D, Van den Berghe G. Cholestatic liver (dys) function during sepsis and other critical illnesses. Intensive Care Med. 2016;42(1):16–27. doi:10.1007/s00134-015-4054-0
   PubMed Web of Science ®Google Scholar
• Ramadori G, Christ B. Cytokines and the hepatic acute-phase response. Semin Liver Dis. 1999;19(2):141–155. doi:10.1055/s-2007-1007106
   PubMed Web of Science ®Google Scholar
• Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340(6):448–454. doi:10.1056/NEJM199902113400607
   PubMed Web of Science ®Google Scholar
• Sasaki M, Ikeda H, Yamaguchi J, Miyakoshi M, Sato Y, Nakanuma Y. Bile ductular cells undergoing cellular senescence increase in chronic liver diseases along with fibrous progression. Am J Clin Pathol. 2010;133(2):212–223. doi:10.1309/AJCPWMX47TREYWZG
   PubMed Web of Science ®Google Scholar
• Ferreira-Gonzalez S, Lu WY, Raven A, et al. Paracrine cellular senescence exacerbates biliary injury and impairs regeneration. Nat Commun. 2018;9(1):1020. doi:10.1038/s41467-018-03299-5
   PubMedGoogle Scholar
• Sasaki M, Ikeda H, Haga H, Manabe T, Nakanuma Y. Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss. J Pathol. 2005;205(4):451–459. doi:10.1002/path.1729
   PubMed Web of Science ®Google Scholar
• Liu R, Xu W, Zhu H, Dong Z, Dong H, Yin S. Aging aggravates Acetaminophen-induced acute liver injury and inflammation through inordinate C/EBPα-BMP9 crosstalk. Cell Biosci. 2023;13(1):61. doi:10.1186/s13578-023-01014-6
   PubMed Web of Science ®Google Scholar