1. Cutting edge: cyclooxygenase-2 activation suppresses Th1 polarization in response to Helicobacter pylori
- Author
-
Keith T. Wilson, Alain P. Gobert, Frank Meyer, Stephen P. James, and Kalathur S. Ramanujam
- Subjects
medicine.medical_treatment ,Immunology ,Down-Regulation ,Peripheral blood mononuclear cell ,Dinoprostone ,Interferon-gamma ,Immune system ,Th2 Cells ,medicine ,Cyclic AMP ,Immunology and Allergy ,Humans ,Cells, Cultured ,Lamina propria ,biology ,Helicobacter pylori ,Membrane Proteins ,Th1 Cells ,biology.organism_classification ,Interleukin-12 ,Growth Inhibitors ,Interleukin-10 ,Up-Regulation ,Enzyme Activation ,Isoenzymes ,Cytokine ,medicine.anatomical_structure ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Second messenger system ,biology.protein ,Leukocytes, Mononuclear ,Cyclooxygenase ,Gastritis ,medicine.symptom - 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 PGE2 release in response to H. pylori preparations. Addition of COX-2 inhibitors or an anti-PGE2 Ab resulted in a marked increase in H. pylori-stimulated IL-12 and IFN-γ production, and a decrease in IL-10 levels. Addition of PGE2 or cAMP, the second messenger activated by PGE2, had the opposite effect. Similarly, stimulated cell proliferation was increased by COX-2 inhibitors or anti-PGE2 Ab, and was decreased by PGE2. 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.
- Published
- 2003