The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation in Helicobacter pylori-associated gastritis
Qiao Yu1, Huiying Shi1, Zhen Ding1
1Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Tripartite motif (TRIM) 31 negatively regulates NLRP3 inflammasome activation in Helicobacter pylori-associated gastritis. TRIM31 deficiency enhances reactive oxygen species and impairs autophagy in gastric cells.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Helicobacter pylori (Hp) infection triggers NLRP3 inflammasome activation, a key factor in gastritis.
- The role of Tripartite motif (TRIM) 31 in Hp-induced NLRP3 inflammasome activation remains unclear.
Discussion:
- TRIM31 expression is reduced during Hp infection.
- TRIM31 acts as a negative regulator of NLRP3 inflammasome activation.
- TRIM31 influences reactive oxygen species (ROS) levels and autophagy flux in gastric epithelial cells.
Key Insights:
- TRIM31 deficiency in gastric cells leads to increased ROS and impaired autophagy.
- Reduced lysosomal cathepsin B and D expression is observed in TRIM31-deficient cells.
- Inhibiting ROS decreases NLRP3 inflammasome expression, highlighting its role in TRIM31's regulatory mechanism.
Outlook:
- Further research could explore therapeutic strategies targeting the TRIM31-ROS-autophagy axis.
- Investigating TRIM31's precise molecular interactions within the inflammasome pathway is warranted.
- Understanding TRIM31's role may offer new avenues for managing Hp-associated gastritis.
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