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 |
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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 |
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