Background: Helicobacter pylori (H. pylori) infection is associated with chronic gastritis, peptic ulceration and gastric carcinoma. Protease-activated receptor-2 (PAR-2), which is activated by trypsin, induced the activation of mitogen-activated protein kinases (MAPK), cell proliferation and apoptosis in several cells. Previously, we found that H. pylori induces the expression of PAR-2, which mediates the expression of adhesion molecules integrins in gastric epithelial cells. In the present study, the role of PAR-2 on H. pylori-induced cell death was investigated by determining cell viability, DNA fragmentation, and the activation of MAPK in gastric epithelial AGS cells.Methods: AGS cells were cultured in the presence of H. pylori transfected with PAR-2 antisense (AS) oligonucleotide (ODN) or treated with a soybean trypsin inhibitor (SBTI). Viable cells and DNA fragmentation were determined by trypan blue exclusion assay and the amount of oligonucleosome-bound DNA, respectively. The activation of MAPK such as extracellular signal-regulated kinases (ERK), p38, and c-Jun N-terminal kinases (JNK), was assessed by Western blotting for phospho-specific forms of MAPK.Results: H. pylori-induced cell death and DNA fragmentation augmented in the cells transfected with PAR-2 AS ODN or treated with SBTI. The activation of MAPK, induced by H. pylori, were suppressed by transfection with PAR-2 AS ODN or treatment with SBTI.Conclusion: PAR-2, whose expression is induced by H. pylori, may prevent cell death and DNA fragmentation with the activation of MAPK in gastric epithelial cells.
Bibliographical noteFunding Information:
This work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006-353-E00008) (to J. W. Lim) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0001669, 2010-0002916) (to H. Kim). H. Kim is grateful to the Brain Korea 21 Project, Yonsei University.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)