Role of vacA and cagA inHelicobacter pylori Inhibition of Mucin Synthesis in Gastric Mucous Cells

摘要

The aim of this study was to investigate the effect ofHelicobacter pylori on the function of gastric mucous cells. H. pylori (104 to 107CFU/well) was incubated with the mucin-producing gastric cell line HM02 for 12 and 24 h. Mucin synthesis and secretion were determined by the incorporation ofd-N-[acetyl-14C]glucosamine into intracellular and released high-molecular-weight glycoproteins.cagA-positive, cytotoxin-producing and non-cytotoxin-producing H. pylori strains impaired the incorporation ofd-N-[acetyl-14C]glucosamine into intracellular glycoproteins. Significant inhibition of mucin synthesis was noted after 12 and 24 h of cocultivation with a bacterial load of ≥105 bacteria (bacterium/cell ratio = 0.25). The cagA-positive, cytotoxin-producing strains (HP64, HP57, and HP87) caused significantly stronger inhibition of intracellular mucin synthesis than the cagA-positive, non-cytotoxin-producing strains (HP05, HP83, and HP84). ThecagA-negative, non-cytotoxin-producing strains (HP01, HP04, and HP85) did not affect intracellular mucin synthesis. The results indicate that H. pylori directly impairs mucin synthesis in gastric mucous cells and that cytotoxic cagA-positive strains cause more profound inhibition of mucin synthesis. We suggest that the increased inhibitory effect of cagA-positive, cytotoxin-producing strains on mucin synthesis can be considered one possible factor responsible for the increased risk of developing peptic ulceration with these H. pylori strains.