Inhibitory effect of rebamipide on the neutrophil adherence stimulated by conditioned media from Helicobacter pylori-infected gastric epithelial cells

We investigated the mechanism or mechanisms by which rebamipide protects ag ainst the gastric mucosal inflammation associated with Helicobacter pylori. The production of interleukin (IL)-8 in association with expression of IL- 8 mRNA was greatly increased in the H. pylori-infected Kato III cells in a concentration- and time-dependent manner, whereas the secretion of IL-6 and tumor necrosis factor-cu was not detectable. The increased production of I L-8 and expression of IL-8 mRNA were significantly inhibited by rebamipide (100-1000 mu M) in a concentration-dependent manner. Formyl-methionyl-leucy lphenylalanine (1 nM), as well as conditioned medium (CM) that was produced from H. pylori-infected Kato iii cells, caused an increase in surface expr ession of CD11b on human neutrophils and an increase in neutrophil adhesion to the human umbilical vein endothelial cells. Rebamipide also suppressed the adherence of neutrophils to endothelial cells as well as the expression of CD11b on neutrophils induced by formyl-methionylleucyl-phenylalanine an d CM. Furthermore, CM-induced neutrophil adhesion to the endothelial cells was significantly inhibited by IL-8-neutralizing antibody, suggesting that IL-8 is implicated in the CM-induced neutrophil adhesion to the cultured hu man umbilical vein endothelial cells. It is concluded that rebamipide exert s its preventive effect against H. pylori-evoked gastric mucosal cell infla mmation by inhibition of the neutrophil adherence to the endothelial cells as well as by suppressing the surface expression of CD11b on neutrophils an d the production of proinflammatory cytokine such as IL-8 from gastric epit helial cells.