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H elicobacter pylori vacuolating cytotoxin induces apoptosis via activation of endoplasmic reticulum stress in dendritic cells
Author(s) -
Kim Jung Mogg,
Kim Joo Sung,
Kim Nayoung,
Ko Su Hyuk,
Jeon Jong Ik,
Kim YoungJeon
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12663
Subject(s) - endoplasmic reticulum , unfolded protein response , apoptosis , cytochrome c , microbiology and biotechnology , fragmentation (computing) , helicobacter pylori , dna fragmentation , stimulation , biology , medicine , programmed cell death , biochemistry , endocrinology , ecology
Background and Aim Dendritic cells ( DC s) are observed on the H elicobacter pylori ‐infected gastric mucosa. DC s 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 DC s. Methods Murine and human DC s were generated from specific pathogen‐free C 57 BL /6 mice and human peripheral blood mononuclear cells, respectively. DC s were incubated with purified VacA , after which B ax activation, cytochrome c release, and DNA fragmentation for apoptosis were measured by fluorescent microscopy, immunoblot, and ELISA . ER stress‐related molecules such as GRP 78 and CHOP were analyzed by immunoblot. Results Treatment of DC s with purified H . pylori VacA resulted in the induction of apoptosis. DC stimulation with VacA led to the translocation of cytoplasmic B ax to mitochondria and cytochrome c release from mitochondria. H . pylori VacA induced signals for ER stress early during the stimulation process in DC s. Furthermore, suppression of ER stress resulted in a significant inhibition of the VacA ‐induced apoptosis in DC s. Conclusion These results suggest that ER stress is critical for regulation of DC apoptotic process in response to VacA stimulation.