During progressive chronic kidney disease, toxic substances known as uremic toxins accumulate in body fluids. Uremia toxin has been documented to be involved in most inflammatory reactions, and indoxyl-sulfate (IS) a major serum metabolite of uremia is a key player in this. The mechanism by which uremia toxin establishes it inflammatory activity is scarcely known; however, researchers believes that a clear understanding of this process can serve as a guide to combat the situation. The study was designed to investigate the role played by uremia toxin in intestinal inflammation. SW480 was used as cell lines for this study. Luciferase assay was used to detect the cell viability of different concentrations of IS. RT-qPCR was used to detect the effect of IS on the expression of inflammatory factors. The comet assay was used as a tool to detect DNA damage. Western blot was used to detect the phosphorylation level of ATM/NEMO/NF-kB protein. The IS of 0.09 nM was determined to be the best experimental concentration by luciferase assay. Result showed that IS promotes the expression of inflammatory factors TNF-α and IL-6. In addition, IS led to enhanced DNA damage in cells. IS promoted ATM phosphorylation leading to phosphorylation of NEMO to activate the NF-kB signalling pathway. In conclusion, uremia toxin facilitates inflammation in intestines by activating the ATM/NEMO/ NF-kB signalling pathway in human intestinal epithelial cells.

中文翻译：

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尿毒症毒素通过激活人肠上皮细胞中的ATM / NEMO /NF-B信号传导途径帮助诱导肠道炎症

在进行性慢性肾脏疾病期间，称为尿毒症毒素的有毒物质会积聚在体液中。尿毒症毒素已被证明参与大多数炎症反应，而尿毒症的主要血清代谢产物吲哚酚硫酸盐（IS）是其中的关键因素。尿毒症毒素确定其炎症活性的机制鲜为人知；但是，研究人员认为，对这一过程的清晰了解可以为应对这种情况提供指导。该研究旨在调查尿毒症毒素在肠道炎症中的作用。SW480用作该研究的细胞系。荧光素酶测定法用于检测不同浓度的IS的细胞活力。RT-qPCR用于检测IS对炎性因子表达的影响。彗星试验用作检测DNA损伤的工具。用蛋白质印迹法检测ATM / NEMO / NF-kB蛋白的磷酸化水平。通过荧光素酶测定法将0.09 nM的IS确定为最佳实验浓度。结果表明，IS促进炎症因子TNF-α和IL-6的表达。另外，IS导致细胞中DNA损伤的增强。IS促进ATM磷酸化，导致NEMO磷酸化，从而激活NF-kB信号通路。总之，尿毒症毒素通过激活人肠上皮细胞中的ATM / NEMO / NF-kB信号传导途径促进肠道炎症。结果表明，IS促进炎症因子TNF-α和IL-6的表达。另外，IS导致细胞中DNA损伤的增强。IS促进ATM磷酸化，导致NEMO磷酸化，从而激活NF-kB信号通路。总之，尿毒症毒素通过激活人肠上皮细胞中的ATM / NEMO / NF-kB信号传导途径促进肠道炎症。结果表明，IS促进炎症因子TNF-α和IL-6的表达。另外，IS导致细胞中DNA损伤的增强。IS促进ATM磷酸化，导致NEMO磷酸化，从而激活NF-kB信号通路。总之，尿毒症毒素通过激活人肠上皮细胞中的ATM / NEMO / NF-kB信号传导途径促进肠道炎症。