Helicobacter pylori upregulates prion protein expression in gastric mucosa: a possible link to prion disease.
OBJECTIVE
Pathological prion protein (PrP(sc)) 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 E(2) (PGE(2)), tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1beta) 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, PGE(2), and IL-1beta dose-dependently upregulated PrPc in gastric cells, while TNF-alpha had no effect.


CONCLUSIONS
H pylori infection leads to the upregulation of gastric PrPc expression. This can be linked to H pylori induced hypergastrinemia and increased mucosal PGE(2) and IL-1beta synthesis. H pylori creates a milieu for enhanced propagation of prions in the gastrointestinal tract.
Konturek
Peter C
PC
Department of Medicine I, University Erlangen-Nuremberg, Germany. peter.konturek@med1.imed.uni-erlangen.de
Bazela
Karolina
K
Kukharskyy
Vitaliy
V
Bauer
Michael
M
Hahn
Eckhart G
EG
Schuppan
Detlef
D
D000328:Adult; D000368:Aged; D002460:Cell Line; D005753:Gastric Mucosa / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008875:Middle Aged; D017096:Prion Diseases / Q000209:etiology*; D011328:Prions / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D007375:Interleukin-1; D011328:Prions; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha