The effect of rebamipide on the expression of proinflammatory mediators and apoptosis in human neutrophils by Helicobacter pylori water‐soluble surface proteins

BACKGROUND: Helicobacter pylori infection elicits persistent neutrophil infiltration in gastric mucosa. The expression of cyclooxygenase (COX)-2 and inhibition of apoptosis in the neutrophils could contribute to the pathogenesis of H. pylori infection. Rebamipide, a mucosal protective and ulcer-healing drug, has been known to inhibit neutrophil activation. AIM: To evaluate the effect of rebamipide on the neutrophils activated by H. pylori water-soluble proteins. METHODS: After neutrophils were stimulated with H. pylori water extract (HPWE) or pre-treated with rebamipide, the expression of COX-2 mRNA and protein was assessed by quantitative RT-PCR and Western blotting, respectively. Prostaglandin (PG) E2 synthesis was determined by radioimmunoassay. Neutrophil apoptosis was evaluated by cytosolic oligonucleosome-bound DNA ELISA and caspase-3 activity was measured by the detection of p-nitroanilide after cleavage from labelled substrate. RESULTS: Stimulation with HPWE up-regulated COX-2 expression and PGE2 secretion, and inhibited neutrophil apoptosis. Rebamipide suppressed PGE2 secretion from neutrophils dose-dependently. Rebamipide, however, did not affect neutrophil apoptosis and caspase-3 activity. CONCLUSIONS: Rebamipide effectively suppressed PGE2 secretion from neutrophils activated by H. pylori water-soluble proteins. This is another possible mechanism of gastric mucosal protection by rebamipide.