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首页> 外文期刊>American Journal of Physiology >Differential effects of deoxycholic acid and taurodeoxycholic acid on NF-kappa B signal transduction and IL-8 gene expression in colonic epithelial cells.
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Differential effects of deoxycholic acid and taurodeoxycholic acid on NF-kappa B signal transduction and IL-8 gene expression in colonic epithelial cells.

机译：脱氧胆酸和牛磺脱氧胆酸对结肠上皮细胞中NF-κB信号转导和IL-8基因表达的差异作用。

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摘要

Several effects of bile acids (BAs) on colonic epithelial cells (CECs) have been described, including induction of proliferation and apoptosis. Some of these effects are mediated through activation of the NF-kappa B transcriptional system. In this study, we investigated the molecular mechanisms underlying the BA-induced gene expression in CECs. The human CEC line HT-29 and primary human CECs were treated with dilutions of salts of deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA). NF-kappa B binding activity was analyzed with EMSA, RelA translocation with immunofluorescence, and I kappa B alpha- and RelA-phosphorylation with Western blot analysis. IL-8 mRNA and protein expression were assessed by quantitative PCR and ELISA. Functional impact of NF-kappa B activation was determined by blocking the proteasome activity with MG132 or by preventing IKK activity with a dominant-negative IKK beta delivered by adenoviral dominant-negative (dn) IKK beta (Ad5dnIKK beta). DCA and TDCA induced IL-8 expression in a dose- and time-dependent manner. It is interesting that DCA but not TDCA induced I kappa B alpha-phosphorylation, RelA translocation, and NF-kappa B binding activity. Accordingly, the proteasome inhibitor MG132 blocked DCA- but not TDCA-induced IL-8 gene expression. In contrast, TDCA-induced IL-8 gene expression correlated with enhanced RelA phosphorylation, which was blocked by Ad5dnIKK beta. Our data suggest that DCA-induced signal transduction mainly utilized the I kappa B degradation and RelA nuclear translocation pathway, whereas TDCA primarily induced IL-8 gene expression through RelA phosphorylation. These differences may have implications for the understanding of the pathophysiology of inflammation and carcinogenesis in the gut.
机译：已经描述了胆汁酸（BAs）对结肠上皮细胞（CECs）的几种作用，包括诱导增殖和凋亡。其中一些作用是通过激活NF-κB转录系统介导的。在这项研究中，我们调查了BA诱导CEC中基因表达的分子机制。用脱氧胆酸（DCA）和牛磺脱氧胆酸（TDCA）的盐的稀释液处理人CEC系HT-29和原代人CEC。 NF-κB结合活性用EMSA，RelA易位和免疫荧光分析，IκBα-和RelA-磷酸化用Western blot分析。通过定量PCR和ELISA评估IL-8 mRNA和蛋白质表达。 NF-κB活化的功能影响是通过用MG132阻断蛋白酶体活性或通过用腺病毒显性阴性（dn）IKK beta（Ad5dnIKK beta）传递的显性阴性IKK beta阻止IKK活性来确定的。 DCA和TDCA以剂量和时间依赖性方式诱导IL-8表达。有趣的是，DCA而非TDCA诱导了IκBα-磷酸化，RelA易位和NF-κB结合活性。因此，蛋白酶体抑制剂MG132阻断DCA-但不阻断TDCA-诱导的IL-8基因表达。相反，TDCA诱导的IL-8基因表达与增强的RelA磷酸化相关，后者被Ad5dnIKK beta阻断。我们的数据表明DCA诱导的信号转导主要利用IκB降解和RelA核易位途径，而TDCA主要通过RelA磷酸化诱导IL-8基因表达。这些差异可能对理解肠道炎症和致癌的病理生理有影响。

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