Expression of tumor necrosis factor- alpha -related apoptosis-inducing ligand and its proapoptotic receptors is down-regulated during gastric infection with virulent cagA+/vacAs1+ Helicobacter pylori strains.

BACKGROUND: Infection of the gastric mucosa with Helicobacter pylori leads to increased apoptosis. Cytokines and receptors of the tumor necrosis factor (TNF) family are known to be involved in this process. The role that the death-inducing TNF- alpha -related apoptosis-inducing ligand (TRAIL) and its receptors play, in the context of H. pylori infection, is unknown. METHODS: In 74 H. pylori-infected and 51 H. pylori-uninfected gastric antral biopsy specimens, levels of TRAIL mRNA and TRAIL receptor mRNA were determined quantitatively by TaqMan reverse-transcriptase polymerase chain reaction. Recombinant TRAIL-induced apoptosis was measured in human and rat gastric epithelial cells by end-labeling of DNA with fluorescein-dTUP and by fluorescence-activated cell sorter analysis. RESULTS: In patients infected with cagA+/vacAs1+ H. pylori strains, expression of TRAIL and the proapoptotic receptors TRAIL-R1 and -R2 was down-regulated, whereas expression of the antiapoptotic receptors TRAIL-R3 and -R4 was up-regulated. Furthermore, expression of TRAIL and TRAIL-R1 and -R2 correlated inversely with the severity of gastric inflammation. Significant apoptosis of isolated human gastric epithelial cells and highly enriched rat parietal and chief cells was induced by 100 ng/mL TRAIL. CONCLUSIONS: Down-regulation of the TRAIL system, in the context of H. pylori infection, may limit exaggerated apoptosis of gastric epithelial cells and destruction of tissue and, therefore, may enable H. pylori to maintain its niche.     «

BACKGROUND: Infection of the gastric mucosa with Helicobacter pylori leads to increased apoptosis. Cytokines and receptors of the tumor necrosis factor (TNF) family are known to be involved in this process. The role that the death-inducing TNF- alpha -related apoptosis-inducing ligand (TRAIL) and its receptors play, in the context of H. pylori infection, is unknown. METHODS: In 74 H. pylori-infected and 51 H. pylori-uninfected gastric antral biopsy specimens, levels of TRAIL mRNA and TRAIL recep...     »