Lipopolysaccharide induces overexpression of MUC2 and MUC5AC in cultured biliary epithelial cells: possible key phenomenon of hepatolithiasis.
Bacterial infection, bile stasis, mucin hypersecretion, and an alteration of the mucin profile such as an aberrant expression of gel-forming apomucin (MUC2 and MUC5AC) in the intrahepatic biliary tree are thought to be important in the lithogenesis of hepatolithiasis. So far, there have been no detailed studies linking bacterial infection to altered mucus secretion of biliary epithelium. In this study, the influence of lipopolysaccharide (LPS), a bacterial component, on apomucin expression in cultured murine biliary epithelial cells was examined with emphasis on the participation of tumor necrosis factor (TNF)-alpha. It was found that LPS up-regulated the expression of MUC2 and MUC5AC in cultured murine biliary epithelial cells. LPS also induced the expression of TNF-alpha in biliary epithelial cells and its secretion into the culture medium. The up-regulation of these apomucins was inhibited by pretreatment with TNF-alpha antibody. TNF-alpha alone also induced the overexpression of MUC2 and MUC5AC in cultured biliary epithelial cells. This overexpression was inhibited by pretreatment with calphostin C, an inhibitor of protein kinase C. These findings suggest that LPS can induce overexpression of MUC2 and MUC5AC in biliary epithelial cells via synthesis of TNF-alpha and activation of protein kinase C. This mechanism might be involved in the lithogenesis of hepatolithiasis.
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004926:Escherichia coli; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008107:Liver Diseases / Q000235:genetics* / Q000473:pathology; D051379:Mice; D055262:Mucin-2; D009077:Mucins / Q000235:genetics*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology
D000906:Antibodies; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C