Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan Province 610041, China.
Biochem Biophys Res Commun. 2010 Jun 25;397(2):232-8. doi: 10.1016/j.bbrc.2010.05.090. Epub 2010 May 28.
The innate host defenses at mucosal surfaces are critical in the early stages of urinary tract bacterial infection. Recent studies have shown that uroepithelial cells aid innate immune cells in fighting off infection, although the exact mechanism by which the uroepithilium participates in immunity remains unclear. TLR4 has been implicated to possess antimicrobial activities specific for bladder epithelial cells (BECs). TLR4 promotes secretion of IL-6 and IL-8, mediates inhibition of bladder epithelial cell (BEC) bacterial invasion, and mediates expulsion of uropathogenic Escherichia coli from BECs. In this study, cultured 5637 cells and Balb/C mice were treated with Astragalus polysaccharides (APS) against invading E. coli. To determine the contribution of TLR4 upregulation to immune response, TLR4 expression and bacterial colony numbers were monitored. After 24 h incubation, only 5637 cells treated with 500 microg/ml APS expressed higher levels of TLR4 compared with the untreated group. However, after 48h, all 5637 cells treated by APS showed higher levels of TLR4 expression than the control cells. The TLR4 expression in the bladder and macrophages mice that received APS was higher than that in the controls. Bacterial colonization in 5637 cells and the bladders of mice treated with APS was significantly reduced compared with the controls. These results demonstrate that at certain concentrations, APS can induce increased TLR4 expression in vivo and in vitro. Further, TLR4 expression upregulation can enhance innate immunity during mucosal bacterial infection. The findings establish the use of APS to modulate the innate immune response of the urinary tract through TLR4 expression regulation as an alternative option for UTI treatment.
固有宿主防御在黏膜表面对于尿路感染的早期阶段至关重要。最近的研究表明，尿路上皮细胞有助于先天免疫细胞抵抗感染，尽管尿路上皮参与免疫的确切机制尚不清楚。TLR4 被认为具有针对膀胱上皮细胞（BEC）的抗菌活性。TLR4 促进 IL-6 和 IL-8 的分泌，介导抑制膀胱上皮细胞（BEC）细菌入侵，并介导尿路致病性大肠杆菌从 BEC 中排出。在这项研究中，用黄芪多糖（APS）处理培养的 5637 细胞和 Balb/C 小鼠以抵抗入侵的大肠杆菌。为了确定 TLR4 上调对免疫反应的贡献，监测了 TLR4 表达和细菌菌落数。孵育 24 小时后，只有用 500μg/ml APS 处理的 5637 细胞表达的 TLR4 水平高于未处理组。然而，48 小时后，所有用 APS 处理的 5637 细胞均表现出高于对照组的 TLR4 表达水平。接受 APS 治疗的膀胱和巨噬细胞中的 TLR4 表达高于对照组。与对照组相比，用 APS 处理的 5637 细胞和小鼠的膀胱中的细菌定植明显减少。这些结果表明，在某些浓度下，APS 可以在体内和体外诱导 TLR4 表达增加。此外，TLR4 表达上调可以增强黏膜细菌感染期间的先天免疫。这些发现确立了使用 APS 通过 TLR4 表达调节来调节尿路感染的先天免疫反应作为 UTI 治疗的替代选择。
