Down-regulation of Bcl-2 is mediated by NF-κB activation in Helicobacter pylori-induced apoptosis of gastric epithelial cells

Abstract

Objective. Bcl-2 family is involved in the regulation of apoptosis. NF-κB activation is associated with either the expression of Bcl-2 or down-regulation of Bcl-2 depending on cell types and stimuli. Previously, we showed NF-κB activation, decrease in the level of Bcl-2, and apoptosis in Helicobacter pylori (H. pylori)-infected gastric epithelial cells. The present study aims to investigate the relation of Bcl-2 expression and NF-κB activation in H. pylori-induced apoptotic cell death of AGS (gastric adenocarcinoma) cells. Material and methods. AGS cells were transfected with mutant IκBα to suppress NF-κB activation or Bcl-2 gene to induce overexpression of Bcl-2. mRNA expression of Bcl-2, p53 and Bax, DNA fragmentation, cell viability, and the numbers of apoptotic cells were determined. Results. H. pylori induced decrease in Bcl-2, but increase in p53 and Bax at the levels of mRNA and protein in AGS cells. H. pylori-induced increment of apoptotic cells and decrease in Bcl-2 level were inhibited in the cells transfected with mutant IκBα gene as compared with the cells transfected with control vector. H. pylori-induced apoptosis determined by apoptotic cells, DNA fragmentation, and cell viability was inhibited in the cells transfected with Bcl-2 gene. Conclusion. Down-regulation of Bcl-2 is mediated by NF-κB activation, which may be the underlying mechanism of apoptosis in H. pylori-infected gastric epithelial cells.

Key Words::

• Apoptosis
• Bcl-2
• Helicobacter pylori
• NF-κB

Acknowledgement

This study was supported by a grant (Joint Research Project under the Korea-Japan Basic Scientific Cooperation Program) from NRF (F01-2009-000-10101-0) and the grants from Basic Science Research Program through NRF funded by the Ministry of Education, Science and Technology (2010-0001669, 2010-0002916). H. Kim is grateful to the Brain Korea 21 Project, college of Human Ecology, Yonsei University.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.