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Infection and Immunity, February 2001, p. 816-821, Vol. 69, No. 2
Departments of Infectious
Diseases1 and Internal
Medicine,2 Tokai University School of Medicine,
Isehara 259-1193, and Department of Microbiology, Yamaguchi
University School of Medicine, Ube 755-8505,3
Japan
Received 24 August 2000/Returned for modification 26 October
2000/Accepted 16 November 2000
The mechanism by which Helicobacter pylori induces
apoptosis remains unclear. In a previous study using biopsy samples, we found a significant correlation between the urease activity of an
H. pylori strain and the apoptosis level induced by this
strain. Therefore, in this study, we investigated whether urease and/or the ammonia generated by urease can induce apoptosis. Human gastric epithelial cell lines were cocultured with H. pylori, and
the levels of apoptosis and ammonia production were measured. The medium was supplemented (or not supplemented) with urea and cytokines. While a large amount of ammonia (>30 mM) accumulated in the coculture containing urease-positive H. pylori and urea, no
significant degree of apoptosis occurred. In the presence of tumor
necrosis factor alpha (TNF-
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.2.816-821.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Ammonia as an Accelerator of Tumor Necrosis
Factor Alpha-Induced Apoptosis of Gastric Epithelial Cells in
Helicobacter pylori Infection
), however, a marked acceleration of
apoptosis was found in this coculture. Such enhancement of apoptosis
was also induced by the addition of 4 to 8 mM ammonia to the cell culture without either H. pylori or urea but containing
TNF-
. These results suggested that ammonia accelerates
cytokine-induced apoptosis in gastric epithelial cells, while ammonia
or urease molecules alone are unable to induce a significant degree of apoptosis.
*
Corresponding author. Mailing address: Department of
Infectious Diseases, Tokai University School of Medicine, Isehara,
Kanagawa 259-1193, Japan. Phone: 0463-93-1121, ext. 2591. Fax:
0463-94-2976.
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