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Expression of Cyclooxygenase-2 in Human Neutrophils Activated by Helicobacter pylori Water-Soluble Proteins: Possible Involvement of NF-κB and MAP Kinase Signaling Pathway

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Abstract

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.

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Authors and Affiliations

  1. Department of Internal Medicine, Liver Research Institute, and Clinical Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

    Joo Sung Kim, Hyun Chae Jung & In Sung Song

  2. Department of Microbiology and Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Korea

    Jung Mogg Kim

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Kim, J.S., Kim, J.M., Jung, H.C. et al. Expression of Cyclooxygenase-2 in Human Neutrophils Activated by Helicobacter pylori Water-Soluble Proteins: Possible Involvement of NF-κB and MAP Kinase Signaling Pathway. Dig Dis Sci 46, 2277–2284 (2001). https://doi.org/10.1023/A:1011939704802

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