title: Helicobacter pylori vacuolating cytotoxin induces apoptosis via activation of endoplasmic reticulum stress in dendritic cells.
abstract: OBJECTIVE
  Dendritic cells (DCs) are observed on the Helicobacter pylori-infected gastric mucosa. DCs generally play an important role in the regulation of inflammation. Although stimulation of gastric epithelial cells with H. pylori vacuolating cytotoxin (VacA) has been reported to induce apoptosis and endoplasmic reticulum (ER) stress, the effects of VacA on the DC apoptotic response have not been well elucidated. This study was conducted to investigate the role of H. pylori VacA on the apoptotic process and ER stress in DCs.
  
  
  METHODS
  Murine and human DCs were generated from specific pathogen-free C57BL/6 mice and human peripheral blood mononuclear cells, respectively. DCs were incubated with purified VacA, after which Bax activation, cytochrome c release, and DNA fragmentation for apoptosis were measured by fluorescent microscopy, immunoblot, and ELISA. ER stress-related molecules such as GRP78 and CHOP were analyzed by immunoblot.
  
  
  RESULTS
  Treatment of DCs with purified H. pylori VacA resulted in the induction of apoptosis. DC stimulation with VacA led to the translocation of cytoplasmic Bax to mitochondria and cytochrome c release from mitochondria. H. pylori VacA induced signals for ER stress early during the stimulation process in DCs. Furthermore, suppression of ER stress resulted in a significant inhibition of the VacA-induced apoptosis in DCs.
  
  
  CONCLUSIONS
  These results suggest that ER stress is critical for regulation of DC apoptotic process in response to VacA stimulation.
authors.affiliation: Department of Microbiology, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Jung Mogg
authors.initials: JM
authors.lastname: Kim
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Su Hyuk
authors.initials: SH
authors.lastname: Ko
authors.forename: Jong Ik
authors.initials: JI
authors.lastname: Jeon
authors.forename: Young-Jeon
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001426:Bacterial Proteins / Q000502:physiology*; D003713:Dendritic Cells / Q000473:pathology* / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D005753:Gastric Mucosa / Q000166:cytology; D006360:Heat-Shock Proteins / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D008810:Mice, Inbred C57BL; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; C074689:VacA protein, Helicobacter pylori; D051742:Transcription Factor CHOP
keywords: ER stress; H. pylori vacuolating cytotoxin; apoptosis; dendritic cells