Soluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells

Ma, Chunling and Yang, Xiaoming and Lv, Qiulan and Yan, Zhimei and Chen, Zeqing and Xu, Daxing and Liu, Xiu and Yang, Wan and Xing, Shichao (2020) Soluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells. Iranian Journal of Basic Medical Sciences, 23 (6). pp. 744-750.

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Abstract

Objective(s): Hyperuricemia is a risk for cardiovascular and metabolic diseases, but the mechanism is ambiguous. Increased intestinal permeability is correlated with metabolic syndrome risk factors. Intestinal epithelial cells play a pivotal role in maintaining intestinal permeability. Uric acid is directly eliminated into intestinal lumen, however, the mechanism and effect of uric acid on intestinal epithelial cells is poorly explored. Here we carried out an analysis to identify the effect and mechanism of uric acid on intestinal epithelial cells.Materials and Methods: IEC-6 was exposed to different concentrations of uric acid to simulate the effect of uric acid on intestinal epithelial cells. Cell viability was determined by MTS assay. Protein content and mRNA were assessed using Western blotting and Q-PCR, respectively. Intracellular ROS was determined using flow-cytometry and fluorescence microscopy. Mitochondrial membrane potential was detected by immunofluorescence using a mitochondrial membrane potential assay kit with JC-1. Small interfering RNA transfection was used to suppress the expression of TLR4.Results: We found soluble uric acid alone increased the release of ROS, depolarized the mitochondrial membrane potential, up-regulated TSPO, increased the expression of TLR4 and NLRP3, and then activated NLRP3 inflammasome and NF-κB signaling, which further resulted in lower expression of tight junction protein and exerted adverse effects on intestinal epithelial cells. Furthermore, the elevated IL-1β could be restored by silencing of TLR4, indicating soluble uric acid induces inflammation via the TLR4/NLRP3 pathway.Conclusion: Soluble uric acid exerted detrimental effect on intestinal epithelial cells through the TLR4/NLRP3 pathway.

Item Type: Article
Uncontrolled Keywords: Hyperuricemia,Inflammasome,Intestinal epithelium,Mechanism,ROS
Subjects: QV pharmacology
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 23 Jun 2020 09:48
Last Modified: 23 Jun 2020 09:48
URI: http://eprints.mums.ac.ir/id/eprint/19284

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