The NLRP3 inflammasome activation is the molecular basis of Helicobacter pylori (Hp)-associated gastritis. Tripartite motif (TRIM) 31 is involved in diverse pathological events. However, whether TRIM31 plays a role in the activation of NLRP3 inflammasome in Hp infection is not clarified. A mouse model of chronic Hp infection was established, and the gastric tissues were subjected to the polymerase chain reaction, western blotting, histopathological analysis, and RNA sequencing. The mitochondrial membrane potential and ROS in the human gastric epithelium GES-1 cells with or without Hp infection were measured by flow cytometry. GES-1 cells with or without TRIM31 knockdown were transfected with mCherry-EGFP-LC3 adenovirus. After rapamycin and bafilomycin A1 stimulation, autophagy flux in the above primed GES-1 cells was assessed by laser confocal microscope. Lysosomal acidification and expression levels of cathepsin B and cathepsin D in GES-1 cells with Hp infection were measured. NLRP3 inflammasome was activated in the gastric tissues of mice with chronic Hp infection in vivo and the GES-1 cells with Hp infection in vitro. TRIM31 was downregulated in Hp infection. TRIM31 negatively regulated the NLRP3 inflammasome activation. Enhanced ROS, impaired autophagy flux, and decreased expression of lysosomal cathepsin B and cathepsin D were observed in TRIM31-deficient GES-1 cells with Hp infection. In turn, inhibition of ROS led to the decreased expression of NLRP3 inflammasome. Together, our data identified that TRIM31 negatively regulated the activation of NLRP3 inflammasome in Hp-associated gastritis by affecting ROS and autophagy of gastric epithelial cells.

中文翻译：

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E3 泛素连接酶 TRIM31 通过调节 ROS 和自噬减弱幽门螺杆菌相关胃炎中 NLRP3 炎症小体的激活

NLRP3 炎性体激活是幽门螺杆菌 (Hp) 相关胃炎的分子基础。三方基序 (TRIM) 31 参与多种病理事件。然而，TRIM31 是否在 Hp 感染中激活 NLRP3 炎性体中发挥作用尚不清楚。建立慢性Hp感染小鼠模型，对胃组织进行聚合酶链反应、蛋白质印迹、组织病理学分析和RNA测序。通过流式细胞术测量有或没有 Hp 感染的人胃上皮 GES-1 细胞中的线粒体膜电位和 ROS。用 mCherry-EGFP-LC3 腺病毒转染具有或不具有 TRIM31 敲低的 GES-1 细胞。在雷帕霉素和巴弗洛霉素 A1 刺激后，通过激光共聚焦显微镜评估上述引发的 GES-1 细胞中的自噬通量。测量了 Hp 感染的 GES-1 细胞中溶酶体酸化和组织蛋白酶 B 和组织蛋白酶 D 的表达水平。NLRP3 炎症小体在体内慢性 Hp 感染小鼠的胃组织和体外 Hp 感染的 GES-1 细胞中被激活。TRIM31 在 Hp 感染中下调。TRIM31 负向调节 NLRP3 炎性体激活。在 Hp 感染的 TRIM31 缺陷 GES-1 细胞中观察到 ROS 增强、自噬通量受损以及溶酶体组织蛋白酶 B 和组织蛋白酶 D 表达降低。反过来，ROS 的抑制导致 NLRP3 炎性体的表达降低。一起，