Cutting Edge: Cyclooxygenase-2 Activation Suppresses Th1 Polarization in Response toHelicobacter 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 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.

Induction of COX-2 expression by Helicobacter pylori is mediated by activation of epidermal growth factor receptor in gastric epithelial cells

“…We also observed increased apoptosis in response to H. pylori infection when gastric epithelial cells were treated with a COX-2 inhibitor and also in ImSt COX-2 Ϫ/Ϫ cells. Increased secretion of PGE 2 may also affect adaptive immunity, since it is known to suppress the T helper 1 (Th1) immune response to bacterial infection (15). Th1-type responses are crucial to control the infection but, at the same time, can promote the development of gastric cancer precursor lesions through the production of IFN-␥ in response to H. pylori (20).…”

Mannose‐capped lipoarabinomannan‐ and prostaglandin E2‐dependent expansion of regulatory T cells in human Mycobacterium tuberculosis infection

“…PGE2 contributes to enhanced growth of respiratory syncytial virus in human airway epithelial cells [32] and to T cell dysfunction from the murine leukemia retrovirus [33]. PGE2 also mediates enhanced growth of Salmonella in macrophages and inhibits the local Th1 response to Helicobacter pylori [34,35]. In addition, during the late phases of murine tuberculosis, high PGE2 concentrations downregulate cell-mediated immunity, favoring disease progression [21].…”

Helicobacter pylori-induced Macrophage Apoptosis Requires Activation of Ornithine Decarboxylase by c-Myc

“…Intriguingly, there is a vigorous gastric mucosal immune response, but this fails to eradicate the organism. H. pylori infection induces a chronic lymphocytic response and an innate immune response in neutrophils, monocytes, and macrophages (2)(3)(4)(5)(6)(7)(8). We have reported several strategies by which the bacterium can avoid host innate immunity by altering macrophage responses to the organism.…”