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Infection and Immunity, February 2001, p. 816-821, Vol. 69, No. 2
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

Muneki Igarashi,1,2 Yukie Kitada,1 Hironori Yoshiyama,3 Atsushi Takagi,2 Takeshi Miwa,2 and Yasuhiro Koga1,*

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-alpha ), 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-alpha . 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.

Infection and Immunity, February 2001, p. 816-821, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.816-821.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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