In vivo and in vitro activation of caspase-8 and -3 associated with Helicobacter pylori infection

Microbes Infect. 2002 Jun;4(7):713-22. doi: 10.1016/s1286-4579(02)01591-5.


In vivo and in vitro studies have shown an increase in apoptosis in gastric epithelial cells in persons infected with Helicobacter pylori. H. pylori-induced activation of caspase-8 and -3 was evaluated using a human gastric adenocarcinoma cell line (AGS) and gastric tissue from humans and monkeys colonized with H. pylori. The enzymatic activity of caspase-8 was detected only in AGS cells exposed to H. pylori up to 24 h. The active form of caspase-8 was present by Western blot after exposure to H. pylori for 3 h and persisted through 24 h. Caspase-3 activity was present in AGS cells exposed to H. pylori for 3 h, reaching a maximum after 24 h (a sevenfold increase in activity). Caspase-8-mediated cleavage of procaspase-3 generated a 20-kDa band (indicative of the presence of active caspase-3) present only in AGS cells exposed to H. pylori. Active caspase-3 staining was markedly increased in gastric mucosa from infected persons and animals, compared to uninfected controls by immunohistochemistry. Stimulation of downstream events leading to apoptosis, such as the cleavage of PARP (poly adenosine-diphosphate-ribose polymerase) and DFF45 (DNA fragmentation factor 45) as a result of activation of caspase-3, was evaluated. PARP was cleaved, resulting in the presence of both an 89- and a 24-kDa band along with DFF45, resulting in the presence of 10- and 12-kDa bands only in gastric cells exposed to H. pylori. Our data show that H. pylori stimulates the activation of caspases and downstream mediators of caspase-induced apoptosis. This suggests that H. pylori-induced apoptosis is mediated through caspase pathways, which include the activation of caspase-8 and subsequent cleavage and activation of caspase-3. This is consistent with caspase-3 activation that was found in the gastric mucosa of humans and monkeys infected with H. pylori.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism*
  • Enzyme Activation
  • Epithelial Cells / enzymology
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Gene Expression Profiling
  • Haplorhini
  • Helicobacter Infections / enzymology*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology*
  • Helicobacter pylori / physiology*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proteins / metabolism
  • Stomach / enzymology
  • Stomach / microbiology*
  • Stomach / pathology
  • Tumor Cells, Cultured


  • DNA fragmentation factor, human
  • Proteins
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases