Upregulation of Mucosal Soluble Fas Ligand and Interferon- May Be Involved in Ulcerogenesis in Patients with Helicobacter pylori-positive Gastric Ulcer

Authors: Shimada M.; Ina K.; Kyokane K.; Imada A.; Yamaguchi H.; Nishio Y.; Hayakawa M.; Iinuma Y.; Ohta M.; Ando T.; Kusugami K.

Source: Scandinavian Journal of Gastroenterology, Volume 37, Number 5, 1 May 2002 , pp. 501-511(11)

Publisher: Informa Healthcare

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Abstract:

Background: Excessive upregulation of gastric epithelial cell apoptosis is speculated to be associated with ulcerogenesis in Helicobacter pylori-positive peptic ulcer disease. H. pylori may have an ulcerogenic effect through induction of gastric epithelial cell apoptosis mediated by infiltrating T cells and their soluble products. Methods: The contents of soluble Fas ligand (sFasL) and interferon- gamma

(IFN-

) in organ cultures and the degree of apoptosis and the expression of apoptosis-related proteins in the gastric epithelium were examined using the mucosal tissues obtained from the antrum and the ulcer site in patients with H. pylori-positive gastric ulcer (GU). The molecular mechanisms of gastric epithelial cell apoptosis induced by sFasL and IFN- gamma

were analyzed using epithelial cell lines, MKN 45 and KATO III. Results: The mucosal tissues of the ulcer site had substantially higher contents of sFasL and IFN- gamma

in organ cultures regardless of its healing stage in association with increased numbers of apoptotic cells and enhanced expression of proapoptotic proteins Bak and Bax in the surface foveolar epithelium as compared with the antral tissues in patients with H. pylori-positive GU. The addition of sFasL caused increases in cytotoxic cell death and caspase-3 activation in MKN 45 and KATO III cells in which IFN- gamma

-treated cells had more prominent effects than untreated cells. The expression of Bak in MKN 45 cells increased when they were treated with IFN- gamma

. Conclusions: Upregulation of mucosal sFasL and IFN- gamma

may be involved in ulcerogenesis in patients with H. pylori-positive GU through induction of gastric epithelial cell apoptosis.

Keywords: APOPTOSIS; CASPASE; GASTRIC ULCER; HELICOBACTER; PYLORI; INTERFERON-GAMMA; SOLUBLE FAS LIGAND

Language: English

Document Type: Research article

Publication date: 2002-05-01

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