Cargando…

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

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 func...

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Jing, Fan, Long, Xiong, Liya, Chen, Peiyu, Wang, Hongli, Chen, Huan, Zhao, Junhong, Xu, Zhaohui, Geng, Lanlan, Xu, Wanfu, Gong, Sitang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283986/
https://www.ncbi.nlm.nih.gov/pubmed/34266494
http://dx.doi.org/10.1186/s40360-021-00509-7
_version_ 1783723307461246976
author Xie, Jing
Fan, Long
Xiong, Liya
Chen, Peiyu
Wang, Hongli
Chen, Huan
Zhao, Junhong
Xu, Zhaohui
Geng, Lanlan
Xu, Wanfu
Gong, Sitang
author_facet Xie, Jing
Fan, Long
Xiong, Liya
Chen, Peiyu
Wang, Hongli
Chen, Huan
Zhao, Junhong
Xu, Zhaohui
Geng, Lanlan
Xu, Wanfu
Gong, Sitang
author_sort Xie, Jing
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8283986
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-82839862021-07-19 Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells Xie, Jing Fan, Long Xiong, Liya Chen, Peiyu Wang, Hongli Chen, Huan Zhao, Junhong Xu, Zhaohui Geng, Lanlan Xu, Wanfu Gong, Sitang BMC Pharmacol Toxicol Research 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. BioMed Central 2021-07-15 /pmc/articles/PMC8283986/ /pubmed/34266494 http://dx.doi.org/10.1186/s40360-021-00509-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Xie, Jing
Fan, Long
Xiong, Liya
Chen, Peiyu
Wang, Hongli
Chen, Huan
Zhao, Junhong
Xu, Zhaohui
Geng, Lanlan
Xu, Wanfu
Gong, Sitang
Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells
title Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells
title_full Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells
title_fullStr Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells
title_full_unstemmed Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells
title_short Rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells
title_sort rabeprazole inhibits inflammatory reaction by inhibition of cell pyroptosis in gastric epithelial cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283986/
https://www.ncbi.nlm.nih.gov/pubmed/34266494
http://dx.doi.org/10.1186/s40360-021-00509-7
work_keys_str_mv AT xiejing rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT fanlong rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT xiongliya rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT chenpeiyu rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT wanghongli rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT chenhuan rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT zhaojunhong rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT xuzhaohui rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT genglanlan rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT xuwanfu rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells
AT gongsitang rabeprazoleinhibitsinflammatoryreactionbyinhibitionofcellpyroptosisingastricepithelialcells