TITLE

INDOMETHACIN ALTERS HELICOBACTER PYLORI INDUCED EFFECTS ON GASTRIC EPITHELIAL CELLS IN VITRO

AUTHOR(S)
James, M.W.; Argent, R.H.; Thomas, R.J.; Hawkey, C.J.; Atherton, J.C.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA51
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction: Helicobacter pylori infection is a major risk factor for distal gastric adenocarcinoma. Pathogenicity determinants include production of an active form of vacuolating cytotoxin (VacA) and possession of the cag pathogenicity island (cag Pal). Toxigenic strains cause marked epithelial cell vacuolation in vitro whilst cag-dependent effects include rearrangement of the actin cytoskeleton to form a "hummingbird" phenotype. NSAID ingestion is associated with a reduced incidence of gastric adenocarcinoma, although mechanisms are unclear We tested the hypothesis that NSAIDs modulate H. pylori-induced effects on epithelial cells, in particular effects induced by VacA and the cag Pal. Methods: AGS cells (1-2 × 10[sup 5] cells/ml) were co-cultured with H pylori strain 60190 (cag+, vacA sl/ml) or its VacA or Cage isogenic mutants at a bacteria:cell ratio of 0.02-70:1. Indomethacin (a non-selective NSAID) or vehicle control was added at a concentration of 0.01-100µM. After overnight incubation with 5% CO[sub 2] at 37°C, vacuolated and hummingbird cells were counted directly using phase contrast microscopy. Statistical analysis was by ANOVA and Student's paired t test. Results: Co-culture with H pylori strain 60190, but not its VacA mutant, increased AGS cell vacuolation from 0.8 ± 0.8 to 25.4 ± 6.5%. Indomethacin had no significant effect in the absence of H pylori, but inhibited H pylori-induced vacuolation in a dose-dependent manner (100µM: by 56 ± 14%, p=0.02; 1 µM:, by 42 ± 15%, p=0.05; 0.01µM: by 26 ± 13% p=0.26). Co-culture with H pylori strain 60190, but not its CagE mutant increased AGS hummingbirds from 0 to 6.2 ± 1.7%. Indomethacin had no effect in the absence of H pylori. In the presence of H pylori, indomethacin at 100µM surprisingly increased hummingbirds by 240 ± 98%, p=0.05. Conclusion: Indomethacin reduces H pylori-induced vacuolation, but in contrast, at...
ACCESSION #
9747617

 

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