title: Cutting edge: cyclooxygenase-2 activation suppresses Th1 polarization in response to Helicobacter pylori.
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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Meyer
authors.forename: Kalathur S
authors.initials: KS
authors.lastname: Ramanujam
authors.forename: Alain P
authors.initials: AP
authors.lastname: Gobert
authors.forename: Stephen P
authors.initials: SP
authors.lastname: James
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
mesh_terms: D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000201:enzymology / Q000382:microbiology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D006131:Growth Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone