title: Expression of tumor necrosis factor- alpha -related apoptosis-inducing ligand and its proapoptotic receptors is down-regulated during gastric infection with virulent cagA+/vacAs1+ Helicobacter pylori strains.
abstract: BACKGROUND
  Infection of the gastric mucosa with Helicobacter pylori leads to increased apoptosis. Cytokines and receptors of the tumor necrosis factor (TNF) family are known to be involved in this process. The role that the death-inducing TNF- alpha -related apoptosis-inducing ligand (TRAIL) and its receptors play, in the context of H. pylori infection, is unknown.
  
  
  METHODS
  In 74 H. pylori-infected and 51 H. pylori-uninfected gastric antral biopsy specimens, levels of TRAIL mRNA and TRAIL receptor mRNA were determined quantitatively by TaqMan reverse-transcriptase polymerase chain reaction. Recombinant TRAIL-induced apoptosis was measured in human and rat gastric epithelial cells by end-labeling of DNA with fluorescein-dTUP and by fluorescence-activated cell sorter analysis.
  
  
  RESULTS
  In patients infected with cagA+/vacAs1+ H. pylori strains, expression of TRAIL and the proapoptotic receptors TRAIL-R1 and -R2 was down-regulated, whereas expression of the antiapoptotic receptors TRAIL-R3 and -R4 was up-regulated. Furthermore, expression of TRAIL and TRAIL-R1 and -R2 correlated inversely with the severity of gastric inflammation. Significant apoptosis of isolated human gastric epithelial cells and highly enriched rat parietal and chief cells was induced by 100 ng/mL TRAIL.
  
  
  CONCLUSIONS
  Down-regulation of the TRAIL system, in the context of H. pylori infection, may limit exaggerated apoptosis of gastric epithelial cells and destruction of tissue and, therefore, may enable H. pylori to maintain its niche.
authors.affiliation: Second Department of Medicine, Technical University of Munich, Munich, Germany. Bruno.Neu@lrz.tum.de
authors.forename: Bruno
authors.initials: B
authors.lastname: Neu
authors.forename: Roland
authors.initials: R
authors.lastname: Rad
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reindl
authors.forename: Mathilde
authors.initials: M
authors.lastname: Neuhofer
authors.forename: Markus
authors.initials: M
authors.lastname: Gerhard
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schepp
authors.forename: Christian
authors.initials: C
authors.lastname: Prinz
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D019872:Chief Cells, Gastric / Q000166:cytology / Q000502:physiology; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology; D008875:Middle Aged; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D000942:Antigens, Bacterial; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; C505644:Tnfrsf10b protein, rat; C505655:Tnfsf10 protein, rat; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C080866:cagA protein, Helicobacter pylori; D004247:DNA