title: Role of vacA and cagA in Helicobacter pylori inhibition of mucin synthesis in gastric mucous cells.
abstract: The aim of this study was to investigate the effect of Helicobacter pylori on the function of gastric mucous cells. H. pylori (10(4) to 10(7) CFU/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 of D-N-[acetyl-(14)C]glucosamine into intracellular and released high-molecular-weight glycoproteins. cagA-positive, cytotoxin-producing and non-cytotoxin-producing H. pylori strains impaired the incorporation of D-N-[acetyl-(14)C]glucosamine into intracellular glycoproteins. Significant inhibition of mucin synthesis was noted after 12 and 24 h of cocultivation with a bacterial load of >/=10(5) 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). The cagA-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.
authors.affiliation: Department of General Pharmacology, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Beil
authors.forename: M L
authors.initials: ML
authors.lastname: Enss
authors.forename: S
authors.initials: S
authors.lastname: Müller
authors.forename: B
authors.initials: B
authors.lastname: Obst
authors.forename: K F
authors.initials: KF
authors.lastname: Sewing
authors.forename: S
authors.initials: S
authors.lastname: Wagner
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000096:biosynthesis*; D015169:Colony Count, Microbial; D003603:Cytotoxins / Q000096:biosynthesis*; D006023:Glycoproteins / Q000096:biosynthesis; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D009077:Mucins / Q000378:metabolism*; D013270:Stomach / Q000166:cytology / Q000382:microbiology*; D014407:Tumor Cells, Cultured
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003603:Cytotoxins; D006023:Glycoproteins; D009077:Mucins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D000117:Acetylglucosamine