Prostaglandin E2 Prevents Helicobacter-Induced Gastric Preneoplasia and Facilitates Persistent Infection in a Mouse Model

Induction of COX-2 expression by Helicobacter pylori is mediated by activation of epidermal growth factor receptor in gastric epithelial 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). A recent report indicated that inhibition of COX-2, which leads to a concomitant reduction in PGE 2 levels, accelerated the development of gastritis and premalignant lesions in a model of H. felis-induced, T cell-driven gastric preneoplasia (20).…”

The C-Terminally Encoded, MHC Class II-Restricted T Cell Antigenicity of the Helicobacter pylori Virulence Factor CagA Promotes Gastric Preneoplasia

“…TCR-b 2/2 mice that lack functional a/b + T cells are protected from gastric cancer precursor lesions, and the adoptive transfer of CD4 + CD25 2 T cells is sufficient to trigger these lesions in resistant mice (24, 27, 30). The pharmacological inhibition of T cell activation prevents and even reverses pre-existing lesions (31,32), and neonatally infected (24) and actively tolerized mice are protected from gastric preneoplasia. Our finding that tolerant mice, despite being colonized very densely by CagA translocation-proficient bacteria, do not develop preneoplasia is perhaps the most important piece of evidence for an indirect pathogenic role of CagA (24).…”

A Double-Edged Sword: Roles of Helicobacter Pylori in Gastric Carcinoma

“…Interestingly, the COX-2 expression induced by H. pylori still seems to be able to attenuate the degree of AG, the initial event of GC, though it plays a role in gastric carcinogenesis (Hahm et al, 2002). COX-2-dependent PGE2 also shows a protective effect during the oncogenic process of Hp-GC in that it can prevent H. pylori-induced gastric preneoplasia and reverse preexisting lesions by suppressing IFN-expression (Toller et al, 2010). As confirmed, the protective effect is always accompanied by increased bacterial colonization in models, which is attributed to the IL-2-dependent immunosuppressive effects of PGE2 on CD4 (+) Th1 cells in migration, proliferation and cytokine secretion.…”

“…As confirmed, the protective effect is always accompanied by increased bacterial colonization in models, which is attributed to the IL-2-dependent immunosuppressive effects of PGE2 on CD4 (+) Th1 cells in migration, proliferation and cytokine secretion. Therefore, PGE2 has an important immunomodulatory role during H. pylori infection, preventing excessive local immune responses and the associated immunopathology by inhibiting the effector functions of pathogenic Th1 cells (Toller et al, 2010). Certain genetic and phenotypic polymorphisms also show beneficial effects in improving the prognosis of GC patients, which might differ in various populations and need further confirmation.…”

“…PGE2, a downstream mediator with central roles in the mentioned COX-2 pathways, plays important functions in both inflammation and carcinogenesis. PGE2 participates in IL-8 production in GECs, facilitates H. pylori colonization and persistent infection, and suppresses the immune functions of CD4 (+) Thelper 1 cells by silencing IL-2 gene transcription, which may help accelerate the tumor formation (Takehara et al, 2006;Toller et al, 2010). During chronic H. pylori infection, there are still excessive amounts of reactive oxygen and nitrogen species containing NO and iNOS, which play crucial roles in the stepwise process of GC (Son et al, 2001;Tiwari et al, 2010).…”