Interaction of omeprazole and Helicobacter pylori-induced nuclear factor-κB activation and mediators in gastric epithelial cells

BackgroundOmeprazole (OMP), a proton pump inhibitor, is a highly effective drug for the management of acid-related disorders. Infections resulting from cytotoxin antigen A (CagA) positive Helicobacter pylori strains have been associated with higher grades of gastric mucosal inflammation. Nuclear factor (NF)-κB activation has been reported to participate in H. pylori-induced gastritis in humans. The complex interaction of OMP on the H. pylori and NF-κB related molecular mechanisms within the gastric mucosa remains unclear. In the present study, we investigated OMP, specifically its effects on NF-κB activation, and COX-2, IL-6, and IL-8 production in gastric cells (Kato-III cells) treated with CagA positive (CagA+) and negative (CagA–) H. pylori strains.MethodsKato-III cells were stimulated with H. pylori water extracts (HPE) containing ATCC 43504 (CagA+) and ATCC 51932 (CagA–) strains. NF-κB activation, inhibitory IκB expression and phosphorylation, and cyclooxygenase (COX)-2, interleukin (IL)-6, and IL-8 expression were assessed in the absence and presence of OMP.ResultsBoth CagA+ and CagA– HPE induced NF-κB activation, whereas OMP suppressed NF-κB activation in the CagA– strain. HPE demonstrated a similar effect on IκB protein expression in the absence and presence of OMP. OMP alone decreased IκB phosphorylation without promoting NF-κB and IκB expression. Additionally, both CagA+ and CagA– HPE induced COX-2 expression, but no significant effect on IL-6 and IL-8. However, OMP downregulated the transcription of COX-2, IL-6, and IL-8 in CagA– HPE treated cells.ConclusionUsing the Kato-III cells model, H. pylori induces NF-κB activation in a CagA-independent manner. Both CagA+ HPE and CagA– HPE induced COX-2 gene expression, but not for IL-6 and IL-8 expression. However, OMP suppressed NF-κB activation via a downregulation of IκB phosphorylation in CagA– HPE treated condition. OMP also suppressed CagA–H. pylori induced-transcription of proinflammatory COX-2, IL-6, and IL-8. OMP may provide different effects on CagA+ and CagA–H. pylori infection conditions.