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

Autor: Lanlan Geng, Wanfu Xu, Long Fan, Hongli Wang, Sitang Gong, Junhong Zhao, Peiyu Chen, Zhaohui Xu, Liya Xiong, Huan Chen, Jing Xie
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Interleukin-1beta
Cell
Anti-Inflammatory Agents
H. pylori infection
chemistry.chemical_compound
0302 clinical medicine
RA1190-1270
Pharmacology (medical)
Child
biology
medicine.diagnostic_test
Interleukin-18
Intracellular Signaling Peptides and Proteins
Pyroptosis
Real-time polymerase chain reaction
medicine.anatomical_structure
Child
Preschool

030220 oncology & carcinogenesis
Rabeprazole
Cell pyroptosis
Female
medicine.drug
Adolescent
RM1-950
Cell Line
Helicobacter Infections
03 medical and health sciences
Western blot
NLRP3
Lactate dehydrogenase
NLR Family
Pyrin Domain-Containing 3 Protein

medicine
Humans
Secretion
Pharmacology
L-Lactate Dehydrogenase
business.industry
Research
Epithelial Cells
Proton Pump Inhibitors
Phosphate-Binding Proteins
Helicobacter pylori
Anti-Ulcer Agents
biology.organism_classification
Molecular biology
030104 developmental biology
chemistry
Gastric Mucosa
Toxicology. Poisons
Therapeutics. Pharmacology
GSDMD
business
Zdroj: BMC Pharmacology and Toxicology, Vol 22, Iss 1, Pp 1-9 (2021)
BMC Pharmacology & Toxicology
ISSN: 2050-6511
Popis: 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.
Databáze: OpenAIRE