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首页> 外文期刊>Life sciences >Toxigenic C. difficile induced inflammatory marker expression by human intestinal epithelial cells is asymmetrical.
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Toxigenic C. difficile induced inflammatory marker expression by human intestinal epithelial cells is asymmetrical.

机译:由人肠上皮细胞产生的毒性艰难梭菌诱导的炎症标志物表达是不对称的。

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摘要

Clostridium difficile infection of the intestinal epithelium and consequent pseudomembranous colitis is an important cause of morbidity and mortality. Pathogenesis has been ascribed exclusively to toxin production. Using in vitro models of human intestinal epithelial layers, we show that exposure to toxigenic C. difficile upregulates epithelial expression of IL-8 and ICAM-1, two molecules important in neutrophil chemoattraction and adhesion and subsequent inflammation. IL-8 production was also stimulated by toxin-containing supernatants. C difficile induced IL-8 release was inhibited by specific antiserum. Increased ICAM-1 expression only occurred after basolateral exposure to C. difficile while apical exposure had no effect on ICAM-1 expression. However, transepithelial electrical resistance was impaired by apical exposure to bacterial suspensions. We suggest that apical exposure to C. difficile induces changes in epithelial layer integrity which allows the bacteria and/or the toxin access to the basolateral compartment where pathogenic inflammatory mechanisms are activated.
机译:艰难梭菌感染的肠上皮和随之而来的伪膜性结肠炎是发病率和死亡率的重要原因。发病机理已专门归因于毒素的产生。使用人类肠道上皮层的体外模型,我们显示暴露于产毒艰难梭菌可上调IL-8和ICAM-1的上皮表达,IL-8和ICAM-1是中性粒细胞趋化和粘附以及随后发炎的两个重要分子。含毒素的上清液也刺激IL-8的产生。艰难梭菌诱导的IL-8释放被特异性抗血清抑制。仅在基底外侧暴露于艰难梭菌后才发生ICAM-1表达增加,而顶端暴露对ICAM-1表达没有影响。然而,经上皮暴露于细菌悬浮液会损害跨上皮电阻。我们建议顶端暴露于艰难梭菌可诱导上皮层完整性的变化,从而使细菌和/或毒素进入活化致病性炎症机制的基底外侧区室。

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