Role of vacA and cagA in Helicobacter pylori inhibition of mucin synthesis in gastric mucous cells.
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.
Beil
W
W
Department of General Pharmacology, Medizinische Hochschule Hannover, D-30625 Hannover, Germany.
Enss
M L
ML
Müller
S
S
Obst
B
B
Sewing
K F
KF
Wagner
S
S
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
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D003603:Cytotoxins; D006023:Glycoproteins; D009077:Mucins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D000117:Acetylglucosamine