Our understanding of biliary epithelial cells (BEC) in physiobiology and immunology has steadily expanded. BEC transports IgA as well as IgM into bile, synthesizes and secretes various chemokines, cytokines, and expresses adhesion molecules involved in cell interaction and signal transduction. These then suggest a myriad of potential roles for BEC in defense from invading microorganisms as well as the pathogenesis of diverse immunologically driven diseases such as primary biliary cirrhosis (PBC), graft-versus-host disease, and primary sclerosing cholangitis (PSC). Despite the progress, there still remain many areas of BEC biology that require further investigation. Most importantly, it remains to be clarified that the extent to which the immunologic activities observed in BEC represent a BEC response to tissue injury or whether BEC themselves are the active participants in the pathogenesis of various cholestatic immunological diseases, including PBC and PSC.

Previous studies have suggested that increased nitric oxide (NO)-mediated products are found in the livers of subjects with primary biliary cirrhosis (PBC), but the mechanisms involved remain enigmatic. We took advantage of immunohistochemistry and several unique monoclonal antibodies to study inflammatory cells responsible for the generation of NO, the enzymes responsible for NO production, the expression of 3-nitrOtyrOSine, and the presence of CD68' and/or myeloperoxidase (MPO) + cells. We examined a total of 1 13 liver specimens, including 64 with PBC, 19 with primary sclerosing cholangitis (PSC), 6 with non-A, non-B hepatitis, 6 with alcoholic liver disease, 4 with cryptogenic cirrhosis, 4 with biliary atresia, and 10 normal subjects. Twentytwo percent of PBC had elevated expression of hitrotyrosine in their bile duct epithelial cells (BECs) (P = ,0316). Furthermore, the BEG in PBC also demonstrated apoptotic changes.MPO-positive inflammatory cells were also noted adjacent to the basement membrane. In contrast, the liver of normal subjects showed few apoptotic changes in the bile ducts, with no evidence of MPO staining in the portal area.

Multiple classes of proteins are modified to tailor them for specific physiological roles. The nature of these posttranslational modifications of proteins, as well as the relationships between them including those of the immune system proteins themselves, and immune system responses are reviewed. Aspects of protein posttranslational modification and their relationship to the pathogenesis of several autoimmune diseases and primary biliary cirrhosis are highlighted.