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

BMC Pharmacol Toxicol. 2021 Jul 15;22(1):44. doi: 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.

Keywords: Cell pyroptosis; GSDMD; H. pylori infection; NLRP3; Rabeprazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Anti-Ulcer Agents / pharmacology
  • Anti-Ulcer Agents / therapeutic use*
  • Cell Line
  • Child
  • Child, Preschool
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Gasdermins
  • Gastric Mucosa / cytology
  • Gastric Mucosa / metabolism
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / metabolism
  • Humans
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Phosphate-Binding Proteins / genetics
  • Phosphate-Binding Proteins / metabolism
  • Proton Pump Inhibitors / pharmacology
  • Proton Pump Inhibitors / therapeutic use*
  • Pyroptosis / drug effects
  • Rabeprazole / pharmacology
  • Rabeprazole / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Anti-Ulcer Agents
  • Interleukin-18
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • L-Lactate Dehydrogenase
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Phosphate-Binding Proteins
  • Proton Pump Inhibitors
  • Rabeprazole
  • GSDMD protein, human
  • Gasdermins
  • NLRP3 protein, human