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

Autor: Nayoung Kim, Jung Mogg Kim, Young-Jeon Kim, Jong Ik Jeon, Joo Sung Kim, Su Hyuk Ko
Rok vydání: 2014
Předmět:
Zdroj: Journal of Gastroenterology and Hepatology. 30:99-108
ISSN: 0815-9319
Popis: 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. 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. Conclusion These results suggest that ER stress is critical for regulation of DC apoptotic process in response to VacA stimulation.
Databáze: OpenAIRE
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