Search

Helicobacter pylori infection elicits persistent neutrophil infiltration in gastric mucosa. The expression of cyclooxygenase (COX) -2 by the neutrophils results in prostaglandin (PG) E2 synthesis, which may account for alterations in tissue homeostasis. In this study, we found that COX-2 mRNA was up-regulated in the neutrophils when stimulated with both H. pylori water extract (HPWE) and live H. pylori in a transwell model and determined by quantitative RT-PCR. PGE2 synthesis was also enhanced in the neutrophils activated by both the HPWE and live H. pylori. A specific COX-2 inhibitor (NS-398) blocked PGE2 synthesis, and an anti-ulcer agent (rebamipide) suppressed it dose dependently. An NF-κB inhibitor (pyrrolidine dithiocarbamate), a MAP kinase (MEK) inhibitor (PD98059), and a p38 MAP kinase inhibitor (SB203580) significantly suppressed the COX-2 gene transcription and PGE2 synthesis in the neutrophils. In conclusion, H. pylori water-soluble proteins may enhance the COX-2 expression, and this action could be mediated through the NF-κB and MAP kinase signaling pathways. The increased section of PGE2 by the neutrophils may play a proinflammatory role in the gastric mucosal response to H. pylori.