Expression of cyclooxygenase-2 in human neutrophils activated by Helicobacter pylori water-soluble proteins: possible involvement of NF-kappaB and MAP kinase signaling pathway.
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-kappaB 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-kappaB 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.
Kim
J S
JS
Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Korea.
Kim
J M
JM
Jung
H C
HC
Song
I S
IS
D001426:Bacterial Proteins / Q000502:physiology*; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D016480:Helicobacter pylori; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013859:Thiocarbamates / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D007527:Isoenzymes; D016328:NF-kappa B; D011725:Pyridines; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020929:Mitogen-Activated Protein Kinase Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one