Helicobacter pylori vacuolating cytotoxin induces apoptosis via activation of endoplasmic reticulum stress in dendritic cells

Jung Mogg Kim, Joo Sung Kim, Nayoung Kim, Su Hyuk Ko, Jong Ik Jeon, Young Jeon Kim

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Background and Aim: 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.pyloriVacA 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.pyloriVacA 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.pyloriVacA 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. Conclusion: These results suggest that ER stress is critical for regulation of DC apoptotic process in response to VacA stimulation.

Original languageEnglish (US)
Pages (from-to)99-108
Number of pages10
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Apoptosis
  • Dendritic cells
  • ER stress
  • H.pylori vacuolating cytotoxin

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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