AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori (H pylon) infection in apoptosis of gastric epithelial cells and to assess the expressi...AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori (H pylon) infection in apoptosis of gastric epithelial cells and to assess the expression of TRAIL on the surface of infiltrating T-cells in Hpylori-infected gastric METHODS: Human gastric epithelial cell lines and primary gastric epithelial cells were co-cultured with H pylori in vitro, then recombinant TRAIL proteins were added to the culture. Apoptosis of gastric epithelial cells was determined by a specific ELISA for cell death. Infiltrating lymphocytes were isolated from Hpyiori-infected gastric mucosa, and expression of TRAIL in T cells was analyzed by flow cytometry.RESULTS: The apoptosis of gastric epithelial cell lines and primary human gastric epithelial cells was mildly increased by interaction with either TRAIL or H pyiorialone. Interestingly,the apoptotic indices were markedly elevated when gastric epithelial cells were incubated with both TRAIL and H pylori(Control vs TRAIL and Hpylori. 0.51±0.06 vs 2.29±0.27,P = 0.018). A soluble TRAIL receptor (DR4-Fc) could specifically block the TRAIL-mediated apoptosis. Further studies demonstrated that infiltrating T-cells in gastric mucosa expressed TRAIL on their surfaces, and the induction of TRAIL sensitivity by H pyloriwas dependent upon direct cell contact of viable bacteria, but not CagA and VacA of H pylori.CONCLUSION: H pylori can sensitize human gastric epithelial cells and enhance susceptibility to TRAIL-mediated apoptosis. Modulation of host cell sensitivity to apoptosis by bacterial interaction adds a new dimension to the immunopathogenesis of H pylori infection.展开更多
基金Supported by the Grants from the National Health Research Institute,Taiwan,NHRI-GI-EX89S942C and the National Science Council,NSC-90-2314B-075B003,NSC 91-2320B-002 and the National Taiwan University Hospital,NTUH 89S2011
文摘AIM: To investigate the relations between tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Helicobacter pylori (H pylon) infection in apoptosis of gastric epithelial cells and to assess the expression of TRAIL on the surface of infiltrating T-cells in Hpylori-infected gastric METHODS: Human gastric epithelial cell lines and primary gastric epithelial cells were co-cultured with H pylori in vitro, then recombinant TRAIL proteins were added to the culture. Apoptosis of gastric epithelial cells was determined by a specific ELISA for cell death. Infiltrating lymphocytes were isolated from Hpyiori-infected gastric mucosa, and expression of TRAIL in T cells was analyzed by flow cytometry.RESULTS: The apoptosis of gastric epithelial cell lines and primary human gastric epithelial cells was mildly increased by interaction with either TRAIL or H pyiorialone. Interestingly,the apoptotic indices were markedly elevated when gastric epithelial cells were incubated with both TRAIL and H pylori(Control vs TRAIL and Hpylori. 0.51±0.06 vs 2.29±0.27,P = 0.018). A soluble TRAIL receptor (DR4-Fc) could specifically block the TRAIL-mediated apoptosis. Further studies demonstrated that infiltrating T-cells in gastric mucosa expressed TRAIL on their surfaces, and the induction of TRAIL sensitivity by H pyloriwas dependent upon direct cell contact of viable bacteria, but not CagA and VacA of H pylori.CONCLUSION: H pylori can sensitize human gastric epithelial cells and enhance susceptibility to TRAIL-mediated apoptosis. Modulation of host cell sensitivity to apoptosis by bacterial interaction adds a new dimension to the immunopathogenesis of H pylori infection.
