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Ma, Chunling, Yang, Xiaoming, Lv, Qiulan, Yan, Zhimei, Chen, Zeqing, Xu, Daxing, Liu, Xiu, Yang, Wan, Xing, Shichao. (1399). Soluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells. , 23(6), 744-750. doi: 10.22038/ijbms.2020.44948.10482
Chunling Ma; Xiaoming Yang; Qiulan Lv; Zhimei Yan; Zeqing Chen; Daxing Xu; Xiu Liu; Wan Yang; Shichao Xing. "Soluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells". , 23, 6, 1399, 744-750. doi: 10.22038/ijbms.2020.44948.10482
Ma, Chunling, Yang, Xiaoming, Lv, Qiulan, Yan, Zhimei, Chen, Zeqing, Xu, Daxing, Liu, Xiu, Yang, Wan, Xing, Shichao. (1399). 'Soluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells', , 23(6), pp. 744-750. doi: 10.22038/ijbms.2020.44948.10482
Ma, Chunling, Yang, Xiaoming, Lv, Qiulan, Yan, Zhimei, Chen, Zeqing, Xu, Daxing, Liu, Xiu, Yang, Wan, Xing, Shichao. Soluble uric acid induces inflammation via TLR4/NLRP3 pathway in intestinal epithelial cells. , 1399; 23(6): 744-750. doi: 10.22038/ijbms.2020.44948.10482

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

Iranian Journal of Basic Medical Sciences
مقاله 6، دوره 23، شماره 6، شهریور 2020، صفحه 744-750    اصل مقاله (632.16 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2020.44948.10482
نویسندگان
Chunling Ma1، 2؛ Xiaoming Yang1؛ Qiulan Lv1، 3؛ Zhimei Yan1؛ Zeqing Chen1؛ Daxing Xu1؛ Xiu Liu1؛ Wan Yang1؛ Shichao Xing* 1، 4
1Medical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. China
2Department of obstctrics, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. China
3Shandong Institute of Orthopaedics and Traumatology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, P. R. China
4School of Cardiovascular Medicine and Science, King’s College London, BHF Centre, London, SE5 9NU, United Kingdom
چکیده
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.
کلیدواژه‌ها
Hyperuricemia؛ Inflammasome؛ Intestinal epithelium؛ Mechanism؛ ROS
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