Rebamipide induces dendritic cell recruitment to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-exposed rat gastric mucosa based on IL-1β upregulation.
ABSTRACT Rebamipide is usually used for mucosal protection, healing of gastric ulcers, treatment of gastritis, etc., but its effects on gastric malignancy have not been elucidated. Using Lewis and Buffalo rat strains treated with peroral administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), we evaluated the effect of rebamipide on the induction of tumor-suppressive dendritic cells, which are known to be heterogeneous antigen-presenting cells of bone marrow origin and are critical for the initiation of primary T-cell responses. Using CD68 as a marker for dendritic cells, the stomach pyloric mucosae of Lewis and Buffalo rats were immunohistochemically analyzed in the presence or absence of rebamipide and MNNG. After a 14-day treatment of rebamipide alone, no significant change in number of CD68-expressing cells was detected in either rat strain. However, after concurrent exposure to MNNG for 14 days, treatment with rebamipide slightly increased CD68-positive cells in the Lewis strain, and significantly increased them in the Buffalo strain. Analysis of two chemotactic factors of dendritic cells, IL-1β and TNF-α, in the gastric cancer cells showed that expression of IL-1β, but not TNF-α, was induced by rebamipide in a dose-dependent manner. A luciferase promoter assay using gastric SH-10-TC cells demonstrated that an element mediating rebamipide action exists in the IL-1β gene promoter region. In conclusion, rebamipide has potential tumor-suppressive effects on gastric tumorigenesis via the recruitment of dendritic cells, based on the upregulation of the IL-1β gene in gastric epithelial cells.
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ABSTRACT: Dendritic cells (DCs) are critical for adaptive immunity and tolerance. Most DCs are strategically positioned as immune sentinels poised to respond to invading pathogens in tissues throughout the body. Differentiated DCs and their precursors also circulate in blood and can get rapidly recruited to sites of challenge. Within peripheral tissues, DCs collect antigenic material and then traffic to secondary lymphoid organs, where they communicate with lymphocytes to orchestrate adaptive immune responses. Hence, the migration and accurate positioning of DCs is indispensable for immune surveillance. Here, we review the molecular traffic signals that govern the migration of DCs throughout their life cycle.Immunity 10/2008; 29(3):325-42. · 19.75 Impact Factor
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ABSTRACT: This study was done to elucidate whether rebamipide during the initial period of acetic acid-induced gastric ulcer affected healing and future ulcer relapse. The cumulative healing rate was higher in rats given rebamipide alone or those given rebamipide and cimetidine during and after administration, but not in rats given cimetidine alone, compared to control rats. Cumulative relapse rate was significantly lower in rats initially given rebamipide alone or those given rebamipide and cimetidine than in rats initially given cimetidine alone. These results suggest that rebamipide is beneficial for obtaining a better quality of ulcer healing and reduction of future ulcer relapse.Digestive Diseases and Sciences 10/1995; 40(11):2469-2472. · 2.55 Impact Factor
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ABSTRACT: Helicobacter pylori infection is related to gastric cancer development, and chronic inflammation is presumed to be the main cause. The aim of the present study was to evaluate the influence of H. pylori cagA, vacA, iceA, and babA genotypes on COX-2, IL-1beta, and IL-8 expression. Of the 217 patients included in the study, 26 were uninfected, 127 had chronic gastritis and were H. pylori-positive, and 64 had gastric cancer. Bacterial genotypes were evaluated by polymerase chain reaction (PCR), and the expression values were determined by quantitative real-time PCR and immunohistochemistry. An association was found between the infection with cagA, vacA s1m1 strains and gastric cancer development. Regarding the 3' region of the cagA gene, we also found an association between the infection with cagA EPIYA-ABCCC strains and clinical outcome. Higher levels of IL-8, IL-1beta, and COX-2 were detected in gastric mucosa from infected patients with chronic gastritis, and they were also associated with the infection by cagA, vacA s1m1 strains. The IL-8 and IL-1beta levels decrease significantly from chronic gastritis to gastric cancer, while the relative expression remained unaltered when COX-2 expression was analyzed among patients with gastritis and cancer. Since inflammatory response to H. pylori infection plays an important role in cellular proliferation and gastric mucosal damage, the up-regulation of IL-1beta, IL-8, and COX-2 in patients with chronic gastritis has an important clinical implication in gastric carcinogenesis.Scandinavian Journal of Gastroenterology 12/2008; 44(2):153-61. · 2.33 Impact Factor