HELICOBACTER-PYLORI UP-REGULATES CYCLOOXYGENASE-2 MESSENGER-RNA EXPRESSION AND PROSTAGLANDIN E-2 SYNTHESIS IN MKN-28 GASTRIC-MUCOSAL CELLS IN-VITRO

Helicobacter pylori has been suggested to play a role in the developme nt of gastric carcinoma in humans. Also, mounting evidence indicates t hat cyclooxygenase-a overexpression is associated with gastrointestina l carcinogenesis. We studied the effect of H. pylori on the expression and activity of cyclooxygenase-l and cyclooxygenase-a in MKN 28 gastr ic mucosal cells. H. pylori did not affect cyclooxygenase-l expression , whereas cyclooxygenase-2 mRNA levels increased by 5-fold at 24 h aft er incubation of MKN 28 cells with broth culture filtrates or bacteria l suspensions from wild-type H. pylori strain. Also, H. pylori caused a S-fold increase in the release of prostaglandin E-2, the main produc t of cyclooxygenase activity. This effect was specifically related to H. pylori because it was not observed with Escherichia coli and was in dependent of VacA, CagA, or ammonia. H. pylori isogenic mutants specif ically lacking picA or picB, which are responsible for cytokine produc tion by gastric cells, were less effective in the up-regulation of cyc looxygenase-a mRNA expression and in the stimulation of prostaglandin E-2 release compared with the parental wild-type strain. This study su ggests that development of gastric carcinoma associated with H. pylori infection may depend on the activation of cyclooxygenase-2-related ev ents.