The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation in Helicobacter pylori-associated gastritis by regulating ROS and autophagy.
The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation in Helicobacter pylori-associated gastritis by regulating ROS and autophagy.
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DOI：
10.1186/s12964-022-00954-9
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发表时间：
2023-01-03
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影响因子：
--
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NLRP3炎症小体激活是幽门螺杆菌(Hp)相关性胃炎的分子基础。三方基序(Trim)31参与多种病理事件。然而，TRIM31是否在幽门螺杆菌感染时NLRP3炎症小体的激活中起作用尚不清楚。建立幽门螺杆菌慢性感染小鼠模型，对胃组织进行聚合酶链式反应、免疫印迹、组织病理学分析和RNA测序。用流式细胞仪检测幽门螺杆菌感染前后人胃上皮细胞线粒体膜电位和ROS的变化。将携带或不携带TRIM31基因敲除的GES-1细胞的mCherry-EGFP-LC3腺病毒分别导入GES-1细胞。用激光共聚焦显微镜检测雷帕霉素和巴菲罗霉素A1刺激后GES-1细胞的自噬通量。检测Hp感染的GES-1细胞溶酶体酸化和组织蛋白酶B、D的表达水平。在体内慢性Hp感染小鼠胃组织和体外Hp感染的GES-1细胞中，NLRP3炎症体被激活。在幽门螺杆菌感染中，TRIM31表达下调。TRIM31负性调节NLRP3炎症体激活。在Hp感染的TRIM31基因缺陷的GES-1细胞中，观察到ROS增强，自噬通量降低，溶酶体组织蛋白酶B和组织蛋白酶D的表达降低。反过来，抑制ROS导致NLRP3炎症体表达减少。总之，我们的数据证实，TRIM31通过影响胃上皮细胞的ROS和自噬，负性调节Hp相关性胃炎中NLRP3炎症小体的激活。视频摘要在线版本包含补充材料，可在10.1186/s12964-022-00954-9查阅。
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. Video abstract The online version contains supplementary material available at 10.1186/s12964-022-00954-9.
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影响因子：
32.4
作者：
Iyer SS;He Q;Janczy JR;Elliott EI;Zhong Z;Olivier AK;Sadler JJ;Knepper-Adrian V;Han R;Qiao L;Eisenbarth SC;Nauseef WM;Cassel SL;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
8.7
作者：
Elliott EI;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1016/s0140-6736(09)60617-6
发表时间：
2009-08-08
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hartgrink HH;Jansen EP;van Grieken NC;van de Velde CJ
通讯作者：
van de Velde CJ
影响因子：
8.7
作者：
Man SM;Kanneganti TD
通讯作者：
Kanneganti TD