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 against 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-alpha was not detectable. The increased production of IL-8 and expression of IL-8 mRNA were significantly inhibited by rebamipide (100-1000 microM) in a concentration-dependent manner. Formyl-methionyl-leucyl-phenylalanine (1 nM), as well as conditioned medium (CM) that was produced from H. pylori-infected Kato III cells, caused an increase in surface expression 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-methionyl-leucyl-phenylalanine and 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 human umbilical vein endothelial cells. It is concluded that rebamipide exerts its preventive effect against H. pylori-evoked gastric mucosal cell inflammation by inhibition of the neutrophil adherence to the endothelial cells as well as by suppressing the surface expression of CD11b on neutrophils and the production of proinflammatory cytokine such as IL-8 from gastric epithelial cells.
Kim
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CD
Department of Pharmacology, College of Medicine, Pusan National University, Pusan, Korea.
Kim
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HH
Hong
K W
KW
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects* / Q000276:immunology; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000502:physiology; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D016133:Polymerase Chain Reaction; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000897:Anti-Ulcer Agents; D000906:Antibodies; D017077:Culture Media, Conditioned; D016207:Cytokines; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D015363:Quinolones; D012333:RNA, Messenger; D009240:N-Formylmethionine Leucyl-Phenylalanine; C052785:rebamipide; D000409:Alanine