Role of the Receptor-Mediated Apoptosis in <i>Helicobacter pylori</i> in Gastric Epithelial Cells

<i>Background and Aims:</i> Two major pathways leading to apoptosis have been described. It has been shown that <i>Helicobacter pylori-</i>mediated apoptosis is mainly effected through the mitochondrial pathway (type II). The role of the type I pathway, including the death receptors, has been discussed controversially. Therefore, we investigated the role of Fas ligand (FasL) and TRAIL in <i>H. pylori-</i>mediated apoptosis by overexpressing antiapoptotic proteins in the human gastric epithelial cell line AGS. <i>Methods:</i> AGS cells overexpressing the antiapoptotic proteins dnFADD, CrmA and Bcl-2 were generated. Apoptosis induced by Fas and <i>H. pylori </i>was monitored by histone ELISA. To investigate the role of TRAIL-mediated apoptosis, AGS cells were transduced with antisense constructs against the proapoptotic TRAIL receptors DR4 and DR5. Protein expression of Fas, TRAIL, DR4, and DR5 was analyzed by Western blot. <i>Results:</i> Fas and <i>H. pylori-mediated </i>apoptosis was significantly inhibited in all generated cell lines, mainly in cells overexpressing CrmA and Bcl-2 with equal effectiveness. In the presence of <i>H. pylori, </i>TRAIL ligand and DR5 receptor were continuously expressed whereas DR4 expression was increasing time dependently. TRAILDR5 antisense significantly reduced <i>H. pylori</i>-mediated apoptosis. <i>Conclusions:</i><i>H. pylori-</i>mediated apoptosis is characterized by activation of either type I or type II pathway. Caspase-8 plays an important role since it triggers the Type II pathway. Fas and TRAIL play an important role in the <i>H. pylori</i>-mediated apoptosis.