In vitro investigations into the role of human intrahepatic biliary epithelial cells as targets in primary biliary cirrhosis
In vitro investigations into the role of human intrahepatic biliary epithelial cells as targets in primary biliary cirrhosis
The work in this thesis examines several aspects of the role of human intrahepatic biliary epithelial cells (HIBECs) as target structures in primary biliary cirrhosis (PBC). HIBECs have been successfully isolated and established in cell culture using the method of Joplin, 1989. A panel of monoclonal antibodies have been generated that stain bile ducts of different sizes in frozen sections of liver tissue. The pattern of staining varies between normal adult human liver tissue and diseased tissue. The pattern of staining seen in these tissue secretions and those of normal foetal liver tissue highlights the heterogeneity of the biliary tree. These findings support the hypothesis that proliferating bile ductules seen in diseases such as PBC might be derived from periseptal hepatocytes.
A 51chromium release cytotoxicity assay has been established and validated. The assay has been used to assess the relative cytotoxicity of a range of bile salts to HIBECs in vitro. Although chenodeoxycholic acid was found to be the most toxic of the bile salts assayed, ursodeoxycholic acid was also toxic to biliary epithelial cells. Furthermore,, ursodeoxycholic acid did not protect from the toxic effects of chenodeoxycholic acid to HIBECs as has been demonstrated for hepatocytes.
Expression of intercellular adhesion molecule-1 (ICAM-1) and HLA class I and II has been demonstrated on HIBECs in vitro. Enhanced expression of ICAM-1 is seen in vitro following stimulation with the proinflammatory cytokines, tumour necrosis factor-α (TNFα), interferon gamma (IFNγ) and interleukin-1 (ILi). Corticosteroids stimulated culture. Expression of HLA class II was also increased following stimulation with proinflammatory cytokines although to a lesser degree. Enhancement of HLA class I expression with cytokines was weak.
University of Southampton
Ayres, Reuben Christopher Simon
2cad2962-dba3-406a-bf72-bb098b73bacf
1993
Ayres, Reuben Christopher Simon
2cad2962-dba3-406a-bf72-bb098b73bacf
Ayres, Reuben Christopher Simon
(1993)
In vitro investigations into the role of human intrahepatic biliary epithelial cells as targets in primary biliary cirrhosis.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The work in this thesis examines several aspects of the role of human intrahepatic biliary epithelial cells (HIBECs) as target structures in primary biliary cirrhosis (PBC). HIBECs have been successfully isolated and established in cell culture using the method of Joplin, 1989. A panel of monoclonal antibodies have been generated that stain bile ducts of different sizes in frozen sections of liver tissue. The pattern of staining varies between normal adult human liver tissue and diseased tissue. The pattern of staining seen in these tissue secretions and those of normal foetal liver tissue highlights the heterogeneity of the biliary tree. These findings support the hypothesis that proliferating bile ductules seen in diseases such as PBC might be derived from periseptal hepatocytes.
A 51chromium release cytotoxicity assay has been established and validated. The assay has been used to assess the relative cytotoxicity of a range of bile salts to HIBECs in vitro. Although chenodeoxycholic acid was found to be the most toxic of the bile salts assayed, ursodeoxycholic acid was also toxic to biliary epithelial cells. Furthermore,, ursodeoxycholic acid did not protect from the toxic effects of chenodeoxycholic acid to HIBECs as has been demonstrated for hepatocytes.
Expression of intercellular adhesion molecule-1 (ICAM-1) and HLA class I and II has been demonstrated on HIBECs in vitro. Enhanced expression of ICAM-1 is seen in vitro following stimulation with the proinflammatory cytokines, tumour necrosis factor-α (TNFα), interferon gamma (IFNγ) and interleukin-1 (ILi). Corticosteroids stimulated culture. Expression of HLA class II was also increased following stimulation with proinflammatory cytokines although to a lesser degree. Enhancement of HLA class I expression with cytokines was weak.
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Published date: 1993
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Local EPrints ID: 462458
URI: http://eprints.soton.ac.uk/id/eprint/462458
PURE UUID: 040a9557-1683-459a-a4a6-25420f11fe60
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Date deposited: 04 Jul 2022 19:08
Last modified: 23 Jul 2022 01:07
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Author:
Reuben Christopher Simon Ayres
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