NR AOVB
AU Konturek,P.C.; Kukharskyy,V.; Bazela,K.; Esslinger,B.; Hahn,E.G.; Schuppan,D.
TI Gastrointestinal inflammations modulate the expression of cellular prion protein (PrPc)
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-15
PT Konferenz-Poster
AB
Background and aims: Pathological prion protein (PrPsc) is responsible for the development of transmissible spongiform encephalopathies (TSE). While PrPsc enters the organisms via the oral route, little is known about the role of gastrointestinal inflammation on the expression of prion precursor PrPc, which is constitutively expressed in the gastrointestinal tract. The aim of the present study was to study PrPc expression in the gastric mucosa of patients with H.pylori gastritis (n=10) before and after eradication therapy (n=10), in small intestinal mucosa of patients with celiac sprue before (n=8) and under a gluten free diet (n=8) and in the colonic mucosa of patients with inflammatory bowel disease (n=10). As controls we recruited healthy age-matched subjects. PrPc mRNA and protein expression was measured by light cycler PCR and quantitative Western blot analysis. In addition, gastric (MKN-45) and colonic (LoVo) cell lines were incubated with key physiological and inflammatory mediators (IL1beta, TNFalpha, TGFbeta1, gastrin, PGE2).
Results: PrPc expression was increased in H.pylori-infection compared with noninfected controls and decreased after successful cure of infection. Gastrin, IL1beta and PGE2 dose-dependently upregulated PrPc expression. In contrast, in patients with sprue and colitis, a significant downregulation of PrPc expression was observed. In LoVo cells PGE2 and TGFbeta-1 dose-dependently downregulated the expression of PrPc.
Conclusion: H. pylori infection leads to upregulation of gastric PrPc expression and this can be linked to H.pylori induced hypergastrinemia and increased mucosal PGE2. In contrast, small intestinal and colonic inflammation is associated with a profound downregulation of PrPc. Patients with H. pylori may carry an increased risk for infection with prions due to PrPc overexpression, whereas patients with enteritis and colitis may be protected against prion infection.
IN Bei mit Helicobacter pylori infizierten Patienten ist die Expression des normalen zellulären Prionproteins PrPc in der Magenschleimhaut gesteigert, während im Gegenteil Entzündungen in Dünndarm und Colon zu reduzierter PrPc-Expression führten. Bei einer Zellinie aus dem Magen ließ sich konzentrationsabhängig die PrPc-Expression durch die Entzündungsmediatoren Gastrin, IL-1ß and PGE2 steigern. Im Gegensatz dazu reduzierten PGE2 und TGFß-1 bei einer Zellinie aus dem Colon die PrPc-Expression.
AD Peter C. Konturek, Vitaliy Kukharskyy, Karolina Bazela, Birgit Esslinger, Eckhart G. Hahn, Detlef Schuppan, First Dept. of Medicine, University Erlangen-Nürnberg
SP englisch
PO Deutschland