title: Helicobacter pylori induces apoptosis in gastric mucosa through an upregulation of Bax expression in humans.
abstract: BACKGROUND
  Maintenance of gastric mucosal integrity depends on the balance between cell loss due to apoptosis and cell proliferation. Helicobacter pylori induces apoptosis in gastric epithelial cells, but the regulation of this process has been little studied. The Bcl-2 proteins are the best-studied family of proteins involved in the mechanism of apoptotic death. Some members of this family, such as Bcl-2, inhibit apoptosis, whereas others, such as Bax, induce it. The present study was performed to determine the apoptosis rate and mRNA and protein expression for Bax and Bcl-2 in the gastric mucosa of duodenal ulcer (DU) patients with H. pylori infection before and after H. pylori eradication. We recruited 8 H. pylori-negative control subjects and 20 DU patients (H. pylori-positive) given a 1-week triple therapy to eradicate H. pylori. The apoptosis was analyzed by means of terminal deoxyribonucleotide transferase-mediated digoxigenin-11-deoxyuridine triphosphate biotin nick-end labeling (TUNEL) staining, and the expression of mRNA for Bax and Bcl-2 by reverse transcription polymerase chain reaction (RT-PCR) and Southern blot. In all patients gastritis was assessed histologically on the basis of the Sydney classification, the presence of H. pylori, and analysis of cagA status.
  
  
  RESULTS
  All 20 DU patients were H. pylori-positive, and 18 (90%) were CagA-positive. The apoptotic cells were infrequently identified in gastric surface epithelium by TUNEL histochemistry in H. pylori-negative controls. In DU patients infected with H. pylori, apoptotic cells were more numerous and seen deep in the gastric glands. The infection was associated with significantly upregulated expression of mRNA and protein for Bax and suppressed mRNA and protein expression for Bcl-2, as determined using RT-PCR and Western blot analysis. The Bax overexpression was significantly stronger in the antrum than in the corpus of H. pylori-infected patients. Four weeks after the eradication a marked decrease of neutrophil infiltration, an improvement of the grade of gastritis (mononuclear infiltration), and significant reduction in apoptosis rate were observed. After eradication the Bax mRNA expression was still at an increased level, whereas the Bcl-2 mRNA expression remained suppressed.
  
  
  CONCLUSIONS
  1) H. pylori induces apoptosis in the gastric epithelium, at least in part, due to an upregulation of proapoptotic Bax and downregulation of antiapoptotic Bcl-2, and 2) Bax mRNA and protein expression was higher in the antrum than in the corpus, and this was probably due to greater inflammatory changes observed in the antrum than in the corpus.
authors.affiliation: Dept. of Internal Medicine I and Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: P C
authors.initials: PC
authors.lastname: Konturek
authors.forename: P
authors.initials: P
authors.lastname: Pierzchalski
authors.forename: S J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: H
authors.initials: H
authors.lastname: Meixner
authors.forename: G
authors.initials: G
authors.lastname: Faller
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.forename: E G
authors.initials: EG
authors.lastname: Hahn
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism; D015139:Blotting, Southern; D015153:Blotting, Western; D004381:Duodenal Ulcer / Q000382:microbiology*; D005753:Gastric Mucosa / Q000473:pathology*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology*; D051028:bcl-2-Associated X Protein
chemical_list: D000942:Antigens, Bacterial; C494826:BAX protein, human; D001426:Bacterial Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C080866:cagA protein, Helicobacter pylori