Affiliation:
1. Departments of Molecular Microbiology and Medical Genetics1 and
2. Pediatrics,2 University of Toronto, and
3. Research Institute, The Hospital for Sick Children,3 Toronto, Canada
Abstract
ABSTRACT
The mechanisms involved in mediating the enhanced gastric epithelial cell apoptosis observed during infection with
Helicobacter 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 a
cagA
-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 with
cagA
-negative,
cagE
-negative, VacA-negative clinical isolates or a
Campylobacter jejuni
strain. In addition to stimulating apoptosis, infection with
H. pylori
enhanced 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 to
H. pylori
infection.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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