Overexpression of Bmi-1 Induces the Malignant Transformation of Gastric Epithelial Cells In Vitro

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.

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In vitro differentiation of Runx3−/–p53−/–gastric epithelial cells into intestinal type cells

Cancer Science ◽

10.1111/j.1349-7006.2008.00732.x ◽

2008 ◽

Vol 99 (4) ◽

pp. 671-676 ◽

Cited By ~ 12

Author(s):

Hiroshi Fukamachi ◽

Ayako Mimata ◽

Issei Tanaka ◽

Kosei Ito ◽

Yoshiaki Ito ◽

...

Keyword(s):

Epithelial Cells ◽

Intestinal Type ◽

Gastric Epithelial Cells ◽

In Vitro Differentiation

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Helicobacter pylori Induces Gastric Epithelial Cell Apoptosis in Association with Increased Fas Receptor Expression

Infection and Immunity ◽

10.1128/iai.67.8.4237-4242.1999 ◽

1999 ◽

Vol 67 (8) ◽

pp. 4237-4242 ◽

Cited By ~ 106

Author(s):

Nicola L. Jones ◽

Andrew S. Day ◽

Hilary A. Jennings ◽

Philip M. Sherman

Keyword(s):

Cell Death ◽

Helicobacter Pylori ◽

Epithelial Cells ◽

Receptor Expression ◽

Gastric Epithelial Cells ◽

Ags Cells ◽

Fas Receptor ◽

Epithelial Cell Apoptosis ◽

H Pylori

ABSTRACT The mechanisms involved in mediating the enhanced gastric epithelial cell apoptosis observed during infection withHelicobacter pylori in vivo are unknown. To determine whether H. pylori directly induces apoptosis of gastric epithelial cells in vitro and to define the role of the Fas-Fas ligand signal transduction cascade, human gastric epithelial cells were infected with H. pylori for up to 72 h under microaerophilic conditions. As assessed by both transmission electron microscopy and fluorescence microscopy, incubation with acagA-positive, cagE-positive, VacA-positive clinical H. pylori isolate stimulated an increase in apoptosis compared to the apoptosis of untreated AGS cells (16.0% ± 2.8% versus 5.9% ± 1.4%, P < 0.05) after 72 h. In contrast, apoptosis was not detected following infection withcagA-negative, cagE-negative, VacA-negative clinical isolates or a Campylobacter jejuni strain. In addition to stimulating apoptosis, infection with H. pylorienhanced Fas receptor expression in AGS cells to a degree comparable to that of treatment with a positive control, gamma interferon (12.5 ng/ml) (148% ± 24% and 167% ± 24% of control, respectively). The enhanced Fas receptor expression was associated with increased sensitivity to Fas-mediated cell death. Ligation of the Fas receptor with an agonistic monoclonal antibody resulted in an increase in apoptosis compared to the apoptosis of cells infected with the bacterium alone (38.5% ± 7.1% versus 16.0% ± 2.8%,P < 0.05). Incubation with neutralizing anti-Fas antibody did not prevent apoptosis of H. pylori-infected cells. Taken together, these findings demonstrate that the gastric pathogen H. pylori stimulates apoptosis of gastric epithelial cells in vitro in association with the enhanced expression of the Fas receptor. These data indicate a role for Fas-mediated signaling in the programmed cell death that occurs in response toH. pylori infection.

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