Macrophage migration inhibitory factor and interleukin-8 produced by gastric epithelial cells during Helicobacter pylori exposure induce expression and activation of the epidermal growth factor receptor.
While a link between Helicobacter pylori exposure and gastric cancer has been established, the underlying mechanisms remain unclear. H. pylori induces a chronic inflammatory response in infected individuals. A link between chronic inflammation and carcinogenesis has long been suggested but never elucidated. Epidermal growth factor receptor (EGFR) signaling plays an important role in both proinflammatory and procarcinogenic mechanisms and is upregulated on gastric epithelial cells (GECs) during H. pylori exposure. The aim of this study was to examine the effects of two important proinflammatory cytokines released during H. pylori infection, macrophage migration inhibitory factor (MIF) and interleukin-8 (IL-8), on the expression and transactivation of EGFR and on the proliferation of GECs during H. pylori exposure. The expression of EGFR by GECs was increased by exposure to either H. pylori, recombinant MIF, or recombinant IL-8. However, cag pathogenicity island knockout strains of H. pylori had very little effect on expression. MIF and IL-8 also induced phosphorylation of EGFR, signaling events, and proliferation during H. pylori exposure, all of which were decreased when they were neutralized by these cytokines or were blocked from their receptors. The overall role of EGFR in these responses to H. pylori exposure was assessed by knocking down EGFR expression by small interfering RNA.
Beswick
Ellen J
EJ
Department of Pediatrics, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.
Reyes
Victor E
VE
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology / Q000502:physiology; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism* / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation
D016209:Interleukin-8; D008263:Macrophage Migration-Inhibitory Factors; D066246:ErbB Receptors