Pc. Konturek et al., Helicobacter pylori induces apoptosis in gastric mucosa through an upregulation of Bax expression in humans, SC J GASTR, 34(4), 1999, pp. 375-383
Background: Maintenance of gastric mucosal integrity depends on the balance
between cell loss due to apoptosis and cell proliferation. Helicobacter py
lori induces apoptosis in gastric epithelial cells, but the regulation of t
his process has been little studied. Tne Bcl-2 proteins are the best-studie
d family of proteins involved in the mechanism of apoptotic death. Some mem
bers of this family, such as Bcl-2, inhibit apoptosis, whereas others, such
as Bar, induce it. The present study was performed to determine the apopto
sis rate and mRNA and protein expression for Bar and Bcl-2 in the gastric m
ucosa of duodenal ulcer (DU) patients with H. pylori infection before and a
fter H. pylori eradication. We recruited 8 H. pylori negative control subje
cts and 20 DU patients (H. pylori-positive) given a 1-week triple therapy t
o eradicate H. pylori. The apoptosis was analyzed by means of terminal deox
yribonucleotide transferase-mediated digoxigenin-11-deoxyuridine triphospha
te biotin nick-end labeling (TUNEL) staining, and the expression of mRNA fo
r Pax and Bcl-2 by reverse transcription polymerase chain reaction (RT-PCR)
and Southern blot. In all patients gastritis was assessed histologically o
n the basis of the Sydney classification, the presence of H. pylori, and an
alysis of cagA status. Results: All 20 DU patients were H. pylori-positive,
and 18 (90%) were CagA-positive. The apoptotic cells were infrequently ide
ntified in gastric surface epithelium by TUNEL histochemistry in H. pylori-
negative controls. In DU patients infected with H. pylori, apoptotic cells
were more numerous and seen deep in the gastric glands. The infection was a
ssociated with significantly upregulated expression of mRNA and protein for
Pax and suppressed mRNA and protein expression for Bcl-2, as determined us
ing RT-PCR and Western blot analysis. The Pax overexpression was significan
tly stronger in the antrum than in the corpus of H. pylori-infected patient
s. Four weeks after the eradication a marked decrease of neutrophil infiltr
ation, an improvement of the grade of gastritis (mononuclear infiltration),
and significant reduction in apoptosis rate were observed. After eradicati
on the Pax mRNA expression was still at an increased level, whereas the Bcl
-2 mRNA expression remained suppressed. Conclusions: 1) H. pylori induces a
poptosis in the gastric epithelium, at least in part, due to an upregulatio
n of proapoptotic Bar and downregulation of antiapoptotic Bcl-2, and 2) Bar
mRNA and protein expression was higher in the antrum than in the corpus, a
nd this was probably due to greater inflammatory changes observed in the an
trum than in the corpus.