Konturek Peter C, Bazela Karolina, Kukharskyy Vitaliy, Bauer Michael, Hahn Eckhart G, Schuppan Detlef
Department of Medicine I, University Erlangen-Nuremberg, Germany.
World J Gastroenterol. 2005 Dec 28;11(48):7651-6. doi: 10.3748/wjg.v11.i48.7651.
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.
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.
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.
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.
病理性朊病毒蛋白（PrP(sc)）是导致传染性海绵状脑病（TSE）的原因。虽然PrPc通过口服途径进入机体，但关于其摄取以及胃肠道炎症对在胃黏膜中组成性表达的朊病毒前体PrPc表达的作用，可用数据较少。
我们使用逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法，研究了10例幽门螺杆菌阳性患者在成功根除幽门螺杆菌前后胃黏膜中PrPc的表达，并与未感染的对照组进行比较。在胃细胞系中分析了胃炎症的中心介质，即胃泌素、前列腺素E(2)（PGE(2)）、肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）对PrPc表达的影响。
与未感染的对照组相比，幽门螺杆菌感染时PrPc表达增加，成功根除后降至正常。胃泌素、PGE(2)和IL-1β在胃细胞中剂量依赖性地上调PrPc，而TNF-α没有影响。
幽门螺杆菌感染导致胃PrPc表达上调。这可能与幽门螺杆菌诱导的高胃泌素血症以及黏膜PGE(2)和IL-1β合成增加有关。幽门螺杆菌为朊病毒在胃肠道中的增强传播创造了环境。
