Helicobacter pylori Up-regulates Cyclooxygenase-2 mRNA Expression and Prostaglandin E2 Synthesis in MKN 28 Gastric Mucosal Cells in Vitro

Abstract

Helicobacter pylori has been suggested to play a role in the development of gastric carcinoma in humans. Also, mounting evidence indicates that cyclooxygenase-2 overexpression is associated with gastrointestinal carcinogenesis. We studied the effect of H. pylori on the expression and activity of cyclooxygenase-1 and cyclooxygenase-2 in MKN 28 gastric mucosal cells. H. pylori did not affect cyclooxygenase-1 expression, whereas cyclooxygenase-2 mRNA levels increased by 5-fold at 24 h after incubation of MKN 28 cells with broth culture filtrates or bacterial suspensions from wild-type H. pylori strain. Also, H. pylori caused a 3-fold increase in the release of prostaglandin E 2 , the main product of cyclooxygenase activity. This effect was specifically related to H. pylori because it was not observed with Escherichia coli and was independent of VacA, CagA, or ammonia. H. pylori isogenic mutants specifically lacking picA or picB, which are responsible for cytokine production by gastric cells, were less effective in the up-regulation of cyclooxygenase-2 mRNA expression and in the stimulation of prostaglandin E 2 release compared with the parental wild-type strain. This study suggests that development of gastric carcinoma associated with H. pylori infection may depend on the activation of cyclooxygenase-2-related events .Helicobacter pylori plays a central role in the etiology of chronic superficial gastritis and peptic ulcer disease and seems to increase the risk for development of gastric adenocarcinoma in humans (1-3). H. pylori-induced gastroduodenal disease depends on the inflammatory response of the host and on the release of a number of virulence factors such as urease, responsible for ammonia generation (4), a vacuolating cytotoxin (VacA) (5), and a cytotoxin-associated immunodominant protein (CagA) (6). In addition, multiple genes in the cag pathogenicity island have recently been described whose expression are necessary for cytokine production by gastric epithelial cells in vitro (7,8). However, the mechanism whereby H. pylori contributes to gastric carcinogenesis is still unknown.Prostaglandins (PGs) 1 are arachidonic acid derivatives that protect the gastric mucosa against exogenous injury (9, 10). PGs synthesis depends on the activity of a constitutively expressed and an inducible PG endoperoxide synthase/cyclooxygenase (COX-1 and COX-2, respectively) (10, 11). Mounting evidence indicates that COX-2 is associated with colorectal carcinogenesis (12, 13), COX-2 being overexpressed in 80 -90% of colorectal adenocarcinomas and in 40 -50% of premalignant adenomas (13). Moreover, COX-2 overexpression has recently been reported in human gastric adenocarcinoma (14). Although the role of COX-2 in gastrointestinal carcinogenesis is still unclear, its up-regulation is probably an early event (13).This study was designed to evaluate whether H. pylori affects COX-1 and COX-2 expression and PGE 2 synthesis in gastric mucosal cells (i.e. MKN 28 cells) (15, 16) in vitro and to study the role of H. pylori virulence factor...

4‐Vinyl‐2,6‐dimethoxyphenol (canolol) suppresses oxidative stress and gastric carcinogenesis in Helicobacter pylori‐infected carcinogen‐treated Mongolian gerbils

“…These results indicate that canolol inhibits the mRNA expression of COX-2, upregulated by H. pylori-infection, and might reduce release of prostaglandin E2 from the gastric mucosa. 26 Canolol also suppressed iNOS activity and presumably the NO endogenously produced by this family of enzymes. It is interesting to note that the numbers of H. pylori colonies in the glandular stomach at 12 weeks postinfection was not significantly reduced.…”

Cutting Edge: Cyclooxygenase-2 Activation Suppresses Th1 Polarization in Response toHelicobacter pylori

“…We and others have shown that H. pylori increases COX-2 expression in human gastric mucosa (14,15) and in gastric epithelial cell lines (21,25). H. pylori is strongly linked to gastric cancer (26), and the chronic inflammation associated with the longstanding infection is presumed to be the main cause.…”

Helicobacter pylori-Induced Invasion and Angiogenesis of Gastric Cells Is Mediated by Cyclooxygenase-2 Induction through TLR2/TLR9 and Promoter Regulation

“…The expression of COX-2 protein is significantly higher in patients with gastric cancer than those with nonulcer dyspepsia (6). Therefore, COX-2 expression is assumed to play a key role in H. pylori-associated gastric cancer in addition to the propagation of gastric inflammation (7). Recent studies have demonstrated that COX-2-mediated PG biosynthesis affects carcinogenesis via several different mechanisms.…”