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

Abstract Background Omeprazole (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. Methods Kato-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. Results Both 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. Conclusion Using 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.