Uremia toxin helps to induce inflammation in intestines by activating the ATM/NEMO/NF-kB signalling pathway in human intestinal epithelial cells

Zhang, Ruibin ; Guo, Feng ; Xue, Xia ; Yang, Ruihong ; Wang, Lihui

Abstract

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.

Keyword(s)

Chronic kidney disease; DNA damage; PCR; Phosphorylation; Toxin

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