Background and aims: Two major pathways leading to apoptosis have been described. It has been shown that Helicobacter pylori-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 H. pylori-mediated apoptosis by overexpressing antiapoptotic proteins in the human gastric epithelial cell line AGS.
Methods: AGS cells overexpressing the antiapoptotic proteins dnFADD, CrmA and Bcl-2 were generated. Apoptosis induced by Fas and H. pylori 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.
Results: Fas and H. pylori-mediated apoptosis was significantly inhibited in all generated cell lines, mainly in cells overexpressing CrmA and Bcl-2 with equal effectiveness. In the presence of H. pylori, TRAIL ligand and DR5 receptor were continuously expressed whereas DR4 expression was increasing time dependently. TRAILDR5 antisense significantly reduced H. pylori-mediated apoptosis.
Conclusions: H. pylori-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 H. pylori-mediated apoptosis.
Copyright 2004 S. Karger AG, Basel.