Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandin E2 synthesis in MKN 28 gastric mucosal cells in vitro.
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 E2, 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 E2 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.
Romano
M
M
Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano",Università Federico II, Via Pansini, 5, 80131 Napoli, Italy.
Ricci
V
V
Memoli
A
A
Tuccillo
C
C
Di Popolo
A
A
Sommi
P
P
Acquaviva
A M
AM
Del Vecchio Blanco
C
C
Bruni
C B
CB
Zarrilli
R
R
D000230:Adenocarcinoma / Q000382:microbiology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D013274:Stomach Neoplasms / Q000382:microbiology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014774:Virulence
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone