Keith Wilson
Faculty Member
Last active: 8/13/2019

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

Sierra JC, Hobbs S, Chaturvedi R, Yan F, Wilson KT, Peek RM, Polk DB
Am J Physiol Gastrointest Liver Physiol. 2013 305 (2): G196-203

PMID: 23681474 · PMCID: PMC3725681 · DOI:10.1152/ajpgi.00495.2012

Chronic infection of the gastric mucosa by Helicobacter pylori is associated with an increased risk of developing gastric cancer; however, the vast majority of infected individuals never develop this disease. One H. pylori virulence factor that increases gastric cancer risk is the cag pathogenicity island, which encodes a bacterial type IV secretion system. Cyclooxygenase-2 (COX-2) expression is induced by proinflammatory stimuli, leading to increased prostaglandin E₂ (PGE₂) secretion by gastric epithelial cells. COX-2 expression is increased in gastric tissue from H. pylori-infected persons. H. pylori also activates the epidermal growth factor receptor (EGFR) in gastric epithelial cells. We now demonstrate that H. pylori-induced activation of COX-2 in gastric cells is dependent upon EGFR activation, and that a functional cag type IV secretion system and direct bacterial contact are necessary for full induction of COX-2 by gastric epithelial cells. PGE₂ secretion is increased in cells infected with H. pylori, and this induction is dependent on a functional EGFR. Increased apoptosis in response to H. pylori occurs in cells treated with a COX-2 inhibitor, as well as COX-2-/- cells, indicating that COX-2 expression promotes cell survival. In vivo, COX-2 induction by H. pylori is significantly reduced in mice deficient for EGFR activation compared with wild-type mice with a fully functional receptor. Collectively, these findings indicate that aberrant activation of the EGFR-COX-2 axis may lower the threshold for carcinogenesis associated with chronic H. pylori infection.

MeSH Terms (12)

Animals Cell Line Cyclooxygenase 2 Dinoprostone Epithelial Cells ErbB Receptors Gene Expression Regulation, Enzymologic Helicobacter Infections Helicobacter pylori Mice Mice, Knockout Stomach

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