Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells

• Main Authors: Jing Xie, Long Fan, Liya Xiong, Peiyu Chen, Hongli Wang, Huan Chen, Junhong Zhao, Zhaohui Xu, Lanlan Geng, Wanfu Xu, Sitang Gong
• Format: Article
• Language: English
• Published: BMC 2021-07-01
• Series: BMC Pharmacology and Toxicology
• Subjects: Rabeprazole; NLRP3; GSDMD; Cell pyroptosis; H. pylori infection
• Online Access: https://doi.org/10.1186/s40360-021-00509-7

Abstract Background Helicobacter pylori (H. pylori) is a common pathogen in development of peptic ulcers with pyroptosis. Rabeprazole, a critical component of standard triple therapy, has been widely used as the first-line regimen for H. pylori infectious treatment. The aim of this study to explore the function of Rabeprazole on cell pyroptosis in vitro. Methods The clinical sample from patients diagnosed with or without H. pylori-infection were collected to analyze by Immunohistochemistry (IHC). Real-time quantitative PCR (qPCR), western blot (WB) and enzyme linked immunosorbent assay (Elisa) were performed to analyze the effect of Rabeprazole on cell pyroptosis, including LDH, IL-1β and IL-18. Results In this study, we showed that Rabeprazole regulated a phenomenon of cell pyroptosis as confirmed by lactate dehydrogenase (LDH) assay. Further results showed that Rabeprazole inhibited cell pyroptosis in gastric epithelial cells by alleviating GSDMD-executed pyroptosis, leading to decrease IL-1β and IL-18 mature and secretion, which is attributed to NLRP3 inflammasome activation inhibition. Further analysis showed that ASC, NLRP3 and Caspase-1, was significantly repressed in response to Rabeprazole stimulation, resulting in decreasing cleaved-caspase-1 expression. Most important, NLRP3 and GSDMD is significantly increased in gastric tissue of patients with H. pylori infection. Conclusion These findings revealed a critical role of Rabeprazole in cell pyroptosis in patients with H. pylori infection, suggesting that targeting cell pyroptosis is an alternative strategy in improving H. pylori treatment.