A Review of the Physiological and Immunological Functions of Biliary Epithelial Cells: Targets for Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis and Drug‐induced Ductopenias

Wu, Chih Te; Davis, Paul A.; Luketic, Velimir A.; Gershwin, M. Eric

doi:10.1080/17402520400004177

Cited by 30 publications

(26 citation statements)

References 61 publications

(49 reference statements)

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“…Total bile production was measured as an indicator of graft metabolic function. Biliary glucose levels were measured as an indicator of biliary epithelial function, with lower glucose levels resulting from increased reabsorption by a functional biliary epithelium …”

Section: Resultsmentioning

confidence: 99%

Damage‐Associated Molecular Patterns Induce Inflammatory Injury During Machine Preservation of the Liver: Potential Targets to Enhance a Promising Technology

et al. 2019

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Machine preservation (MP) has emerged as a promising technology in liver transplantation, but the cellular processes occurring during MP have not been characterized. Recent studies have noted the presence of inflammatory molecules generated during MP. We hypothesized that there is a metabolism‐dependent accumulation of damage‐associated molecular patterns (DAMPs) and inflammatory cytokines during MP and that these molecules provoke inflammation in the graft. To stratify groups by metabolic rate, MP was performed on rat livers from standard donors at 3 different temperatures: room temperature (RT), subnormothermic (30°C), and normothermic (37°C). Static cold storage at 4°C was included as a reference group. Following a 4‐hour preservation period, graft reperfusion was performed ex vivo at 37°C (n = 6 for all groups). Levels of DAMPs and inflammatory cytokines were measured, and their biological activity was assessed by determining toll‐like receptor (TLR) stimulation, inflammatory gene expression, and activation of cell death pathways. There was a time‐dependent increase in levels of DAMPs during MP with high‐mobility group box 1 and extracellular DNA levels increasing for all groups ( P < 0.05, 30 versus 240 minutes). Tumor necrosis factor α levels in the perfusate also increased during MP for all groups ( P < 0.05, 30 minutes versus 240 minutes). Levels of inflammatory molecules correlated with increased activation of TLRs (TLR3, P = 0.02, normothermic machine preservation [MP37] versus machine preservation at room temperature [MPRT]; TLR9, P = 0.02, MP37 versus MPRT). Priming of the NLRP3 inflammasome and activation of cell death pathways were reduced in grafts preserved by MP at room temperature. In conclusion, inflammatory molecules produced during MP have a biological impact on the graft. Therapies to attenuate DAMP‐mediated inflammation during MP may further enhance this promising technology.

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Section: Resultsmentioning

confidence: 99%

Damage‐Associated Molecular Patterns Induce Inflammatory Injury During Machine Preservation of the Liver: Potential Targets to Enhance a Promising Technology

et al. 2019

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“…These cells express and secrete chemokines and cytokines, including interferon gamma, tumor necrosis factor-alpha, and interleukin-1, which are important signaling molecules for biliary innate immune defenses given that they can recruit neutrophils, monocytes, or T lymphocytes, and the recruited immune cells can act as a protective response against biliary tract infections [18]. Conversely, given their relatively high expression of human leukocyte antigen class I-II, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3, biliary epithelial cells are also known to be vulnerable to immune attack [19].…”

Section: Discussionmentioning

confidence: 99%

Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer

et al. 2017

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Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3.0 mg/kg) every 2 weeks until disease progression or irAEs occurred. Clinical data regarding the duration of nivolumab treatment, symptoms, laboratory abnormalities, pathological findings of liver parenchyma biopsy specimens, and management of nivolumab-related cholangitis were analyzed. Results Our analysis revealed that nivolumab-related cholangitis was characterized by (1) localized extrahepatic bile duct dilation without obstruction; (2) diffuse hypertrophy of the extrahepatic bile duct wall; (3) a dominant increase in the biliary tract enzymes alkaline phosphatase and gamma-glutamyl transpeptidase relative to the hepatic enzymes aspartate and alanine aminotransferase; (4) normal or reduced levels of the serum immunological markers antinuclear antibody, antimitochondrial antibody, smooth muscle antibody, and immunoglobulin G4; (5) the pathological finding of biliary tract cluster of differentiation 8-positive T cell infiltration from liver biopsy; and (6) a moderate to poor response to steroid therapy. Conclusions Nivolumab-related cholangitis is associated with distinct imaging and clinicopathological features that distinguish it from acute cholangitis of common etiologies and other immune-related cholangitis. Further studies are warranted to establish the optimal management of patients with this irAE.

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“…Pathological activation can result in inflammation of the bile ducts as in PBC. 24 In genetically susceptible persons suffering from inflammatory bowel diseases, a bimodal activation of innate and adaptive immune responses is known for ulcerative colitis and Crohn disease. Among other organs, skin is involved most frequently presenting with a neutrophilic dermatosis.…”

Section: Discussionmentioning

confidence: 99%

Neutrophilic Epitheliotropism Is a Histopathological Clue to Neutrophilic Urticarial Dermatosis

Broekaert

Böer‐Auer

Kerl

et al. 2016

The American Journal of Dermatopathology

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A Review of the Physiological and Immunological Functions of Biliary Epithelial Cells: Targets for Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis and Drug‐induced Ductopenias

Cited by 30 publications

References 61 publications

Damage‐Associated Molecular Patterns Induce Inflammatory Injury During Machine Preservation of the Liver: Potential Targets to Enhance a Promising Technology

Damage‐Associated Molecular Patterns Induce Inflammatory Injury During Machine Preservation of the Liver: Potential Targets to Enhance a Promising Technology

Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer

Neutrophilic Epitheliotropism Is a Histopathological Clue to Neutrophilic Urticarial Dermatosis

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