Lipopolysaccharide induces overexpression of MUC2 and MUC5AC in cultured biliary epithelial cells - Possible key phenomenon of hepatolithiasis
Lipopolysaccharide induces overexpression of MUC2 and MUC5AC in cultured biliary epithelial cells - Possible key phenomenon of hepatolithiasis
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DOI：
10.1016/s0002-9440(10)64423-9
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发表时间：
2002-10-01
影响因子：
6
通讯作者：
Nakanuma, Y
中科院分区：
文献类型：
--
作者：
Zen, Y;Harada, K;Nakanuma, Y
细菌感染、胆汁淤积、粘蛋白高分泌和粘蛋白谱的改变，如肝内胆管树中凝胶形成apoinucin（MUC 2和MUC 5AC）的异常表达，被认为在肝内胆管结石的结石形成中是重要的。到目前为止，还没有详细的研究将细菌感染与胆管上皮粘液分泌的改变联系起来。在这项研究中，研究了细菌成分脂多糖（LPS）对培养的小鼠胆管上皮细胞中apoinucin表达的影响，重点是肿瘤坏死因子（TNF）-α的参与。结果发现，LPS可上调MUC 2和MUC 5AC的表达。培养的小鼠胆管上皮细胞。LPS还可诱导胆管上皮细胞表达TNF-α。细胞及其分泌物进入培养基。用TNF-α抗体预处理可抑制这些apomucins的上调。单独TNF-α也诱导培养的胆管上皮中MUC 2和MUC 5AC的过表达。细胞这种过度表达可被蛋白激酶C抑制剂calphostin C预处理抑制。这些结果表明，LPS可通过合成TNF-α和激活蛋白激酶C诱导胆管上皮细胞中MUC 2和MUC 5AC的过表达。这一机制可能参与了肝内胆管结石的形成。
Bacterial Infection, bile stasis, mucin hypersecretion, and an alteration of the mucin profile such as an aberrant expression of gel-forming apoinucin (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 apoinucin 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.