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World J Gastroenterol. Dec 28, 2005; 11(48): 7651-7656
Published online Dec 28, 2005. doi: 10.3748/wjg.v11.i48.7651
Helicobacter pylori upregulates prion protein expression in gastric mucosa: A possible link to prion disease
Peter C Konturek, Karolina Bazela, Vitaliy Kukharskyy, Michael Bauer, Eckhart G Hahn, Detlef Schuppan
Peter C Konturek, Karolina Bazela, Vitaliy Kukharskyy, Michael Bauer, Eckhart G Hahn, Detlef Schuppan, Department of Medicine, University of Erlangen-Nuernberg, 91054 Erlangen, Germany
Author contributions: All authors contributed equally to the work.
Supported by Bavarian Ministry of Health, Germany
Correspondence to: Assistant Professor Dr Peter C Konturek, Department of Medicine I, University Erlangen-Nuremberg, Germany. peter.konturek@med1.imed.uni-erlangen.de
Telephone: +49-9131-8535210 Fax: +49-9131-8535212
Received: January 18, 2005
Revised: July 2, 2005
Accepted: July 8, 2005
Published online: December 28, 2005
Abstract

AIM: Pathological prion protein (PrPsc) is responsible for the development of transmissible spongiform encephalopathies (TSE). While PrPc enters the organism via the oral route, less data is available to know about its uptake and the role of gastrointestinal inflammation on the expression of prion precursor PrPc, which is constitutively expressed in the gastric mucosa.

METHODS: We studied PrPc expression in the gastric mucosa of 10 Helicobacter pylori-positive patients before and after successful H pylori eradication compared to non-infected controls using RT-PCR and Western blotting. The effect of central mediators of gastric inflammation, i.e., gastrin, prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) on PrPc expression was analyzed in gastric cell lines.

RESULTS: PrPc expression was increased in H pylori-infection compared with non-infected controls and decreased to normal after successful eradication. Gastrin, PGE2, and IL-1β dose-dependently upregulated PrPc in gastric cells, while TNF-α had no effect.

CONCLUSION: H pylori infection leads to the upregulation of gastric PrPc expression. This can be linked to H pylori induced hypergastrinemia and increased mucosal PGE2 and IL-1β synthesis. H pylori creates a milieu for enhanced propagation of prions in the gastrointestinal tract.

Keywords: Prions; Helicobacter pylori; Gastrin; Pro-inflammatory cytokines