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

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)-kappa B activation has been reported to participate in H. pylori-induced gastritis in humans. The complex interaction of OMP on the H. pylori and NF-kappa B related molecular mechanisms within the gastric mucosa remains unclear. In the present study, we investigated OMP, specifically its effects on NF-kappa B 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-kappa B activation, inhibitory I kappa B expression and phosphorylation, and cyclooxygenase (COX)-2, interleukin (IL)-6, and EL-8 expression were assessed in the absence and presence of OMP. Results: Both CagA(+) and CagA(-) HPE induced NF-kappa B activation, whereas OMP suppressed NF-kappa B activation in the CagA(-) strain. HPE demonstrated a similar effect on I kappa B protein expression in the absence and presence of OMP. OMP alone decreased I kappa B phosphorylation without promoting NF-kappa B and I kappa B expression. Additionally, both CagA(+) and CagA(-) BPE 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-kappa B 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-kappa B activation via a downregulation of I kappa B 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. Copyright (C) 2014 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.