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Increased
Expression of Interleukin-6 and Tumor Necrosis Factor-[alpha] in Pathologic
Biliary Epithelial Cells: In Situ and Culture Study |
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Mitsue Yasoshima,
Naoko Kono, Hiroyuki Sugawara, Kazuyoshi Katayanagi, Kenichi Harada, and
Yasuni Nakanuma |
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Second
Department of Pathology, Kanazawa University School of Medicine, Kanazawa,
Japan |
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We examined the pathologic
significance of the expression of interleukin-6 (IL-6) and tumor necrosis
factor-[alpha] (TNF-[alpha]), both proinflammatory cytokines, on intrahepatic
biliary epithelial cells, using immunohistochemical and in situ hybridization
techniques as well as culture study. IL-6 and TNF-[alpha] were expressed
in the cytoplasm of biliary epithelial cells of damaged small bile ducts
and bile ductules, particularly in primary biliary cirrhosis. Their expression
on the bile ducts was mild to moderate in other hepatobiliary diseases and
mild or absent in normal livers. Signals of IL-6 mRNA and TNF-[alpha] mRNA
were detected in the cytoplasm of biliary epithelial cells, especially in
primary biliary cirrhosis. Immunoelectron microscopic study supported this.
TNF receptor and to a lesser degree IL-6 receptor [alpha]-chain were detected
on these damaged bile ducts, suggesting an autocrine effect. By Western
blotting and enzyme-linked immunosorbent assay, IL-6 and TNF-[alpha] were
frequently detected in gallbladder bile from primary biliary cirrhosis,
and their titers were higher compared with other hepatobiliary diseases.
Culture of intrahepatic biliary epithelial cells revealed that they expressed
IL-6 and secreted IL-6 in the culture media. These results suggest that
the intrahepatic biliary epithelial cells are able to synthesize IL-6 and
probably TNF-[alpha] and are involved in the production of bile duct lesions
by means of receptor-mediated processes, particularly biliary epithelial
proliferation and destruction and autoimmune augmentation, in primary biliary
cirrhosis. |
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