幽门螺杆菌硫氧还蛋白1可能通过IL6/STAT3途径发挥高度致病作用。

Helicobacter pylori Thioredoxin1 May Play a Highly Pathogenic Role via the IL6/STAT3 Pathway.

作者信息

Guo Yanlei, Ding Shigang

机构信息

Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.

出版信息

Gastroenterol Res Pract. 2022 Aug 1;2022:3175935. doi: 10.1155/2022/3175935. eCollection 2022.

DOI:10.1155/2022/3175935

PMID:35958524

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9359846/

Abstract

BACKGROUND

Recent studies have shown that CagA is considered highly pathogenic to helicobacter pylori (HP) in Western populations. However, in East Asia, CagA positive HP can be up to 90%, but not all patients will lead to gastric cancer. Our research group has found that HP thioredoxin1 (Trx1) may be a marker of high pathogenicity. Here, we investigate whether HP Trx1 exerts high pathogenicity and its internal molecular mechanism.

MATERIALS AND METHODS

We constructed the coculture system of high-Trx1 HP and low-Trx1 HP strains with gastric epithelial cell lines separately and detected the influence of HP strains. The cells were stained by AM/PI, and the cell's mortality was assessed by fluorescence microscope. The cell's supernatants or precipitates were collected to detect the expression of IL6. In addition, the cell's precipitates were collected, and the expression of p-STAT3 was detected by western blot. Furthermore, the cell's supernatants were collected for detecting the expression of 8-OHDG to investigate the extent of DNA damage.

RESULTS

The high-Trx1 HP can cause higher mortality of GES-1 cells compared with the low-Trx1 HP group (high-Trx1 HP (4.53 ± 0.56) %, low-Trx1 HP (0.39 ± 0.10) %, < 0.001). The mRNA and protein level of IL-6 in AGS and GES-1 cells were increased during HP infection, and the expression of IL-6 in the High-Trx1 HP group was much higher than the low-Trx1 HP group. Besides, the expression of p-STAT3 was higher in the HP-positive gastric mucosa. And the expression of p-STAT3 in the high-Trx1 HP group was significantly upregulated compared with the low-Trx1 HP group. Furthermore, the expression of 8-OHDG in the high-Trx1 group was much higher than the low-Trx1 group (high-Trx1 HP (5.47 ± 1.73) ng/ml, low-Trx1 HP (2.89 ± 1.72) ng/ml, < 0.05).

CONCLUSION

HP Trx1 may play as a marker of high pathogenicity, and the high-Trx1 HP could mediate the pathogenic process of HP infection via the IL6/STAT3 pathway.

摘要

背景

近期研究表明，在西方人群中，细胞毒素相关基因A（CagA）被认为是幽门螺杆菌（HP）的高致病性因素。然而，在东亚地区，CagA阳性的HP感染率可达90%，但并非所有患者都会发展为胃癌。我们的研究小组发现，HP硫氧还蛋白1（Trx1）可能是高致病性的一个标志物。在此，我们研究HP Trx1是否具有高致病性及其内在分子机制。

材料与方法

我们分别构建了高Trx1 HP菌株和低Trx1 HP菌株与胃上皮细胞系的共培养系统，并检测HP菌株的影响。细胞用AM/PI染色，通过荧光显微镜评估细胞死亡率。收集细胞上清液或沉淀物以检测白细胞介素6（IL6）的表达。此外，收集细胞沉淀物，通过蛋白质免疫印迹法检测磷酸化信号转导子和转录激活子3（p-STAT3）的表达。此外，收集细胞上清液以检测8-羟基脱氧鸟苷（8-OHDG）的表达，以研究DNA损伤程度。

结果

与低Trx1 HP组相比，高Trx1 HP可导致胃黏膜上皮细胞系GES-1细胞更高的死亡率（高Trx1 HP组为（4.53±0.56）%，低Trx1 HP组为（0.39±0.10）%，P<0.001）。在HP感染过程中，AGS和GES-1细胞中IL-6的mRNA和蛋白水平升高，高Trx1 HP组中IL-6的表达远高于低Trx1 HP组。此外，HP阳性胃黏膜中p-STAT3的表达较高。与低Trx1 HP组相比，高Trx1 HP组中p-STAT3的表达显著上调。此外，高Trx1组中8-OHDG的表达远高于低Trx1组（高Trx1 HP组为（5.47±1.73）ng/ml，低Trx1 HP组为（2.89±1.72）ng/ml，P<0.05）。