Abstract
Helicobacter pylori infection causes a Th1-driven mucosal immune response. Cyclooxygenase (COX)-2 is up-regulated in lamina propria mononuclear cells in H. pylori gastritis. Because COX-2 can modulate Th1/Th2 balance, we determined whether H. pylori activates COX-2 in human PBMCs, and the effect on cytokine and proliferative responses. There was significant up-regulation of COX-2 mRNA and PGE(2) release in response to H. pylori preparations. Addition of COX-2 inhibitors or an anti-PGE(2) Ab resulted in a marked increase in H. pylori-stimulated IL-12 and IFN-gamma production, and a decrease in IL-10 levels. Addition of PGE(2) or cAMP, the second messenger activated by PGE(2), had the opposite effect. Similarly, stimulated cell proliferation was increased by COX-2 inhibitors or anti-PGE(2) Ab, and was decreased by PGE(2). Our findings indicate that COX-2 has an immunosuppressive role in H. pylori gastritis, which may protect the mucosa from severe injury, but may also contribute to the persistence of the infection.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cells, Cultured
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Cyclic AMP / pharmacology
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Cyclooxygenase 2
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Dinoprostone / biosynthesis
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Dinoprostone / pharmacology
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Dinoprostone / physiology
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Down-Regulation / drug effects
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Down-Regulation / immunology*
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Enzyme Activation / immunology
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / metabolism
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Growth Inhibitors / physiology
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Helicobacter pylori / immunology*
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Humans
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / biosynthesis
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Interleukin-10 / biosynthesis
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Interleukin-12 / antagonists & inhibitors
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Interleukin-12 / biosynthesis
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Isoenzymes / biosynthesis
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Isoenzymes / metabolism
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Isoenzymes / physiology*
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / enzymology
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Leukocytes, Mononuclear / microbiology
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Membrane Proteins
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Prostaglandin-Endoperoxide Synthases / biosynthesis
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Prostaglandin-Endoperoxide Synthases / metabolism
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Prostaglandin-Endoperoxide Synthases / physiology*
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Th1 Cells / immunology*
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Th1 Cells / metabolism*
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Th1 Cells / microbiology
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Th2 Cells / microbiology
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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Growth Inhibitors
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Isoenzymes
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Membrane Proteins
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Interleukin-10
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Interleukin-12
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Interferon-gamma
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Cyclic AMP
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone