interleukin-8 and sofalcone

Sofalcone has been reported to exert anti-ulcer and gastroprotective actions, but its exact mechanism of action remains unknown. In our laboratory, we found that indomethacin-induced gastric ulcers become worse when associated with Helicobacter pylori infection.. We employed the H. pylori-infected gnotobiotic murine model to examine the effect of sofalcone on indomethacin-induced gastric ulcers in the presence of H. pylori infection. In vitro experiments were also done to evaluate the effects of sofalcone on H. pylori growth, adherence of H. pylori to the MKN45 cells (a human gastric epithelial cell line), and these cells' IL-8 production in the presence of H. pylori.. We found that sofalcone produced a significant improvement in ulcer size as well as a substantial reduction in the number of H. pylori colonies in H. pylori-infected gnotobiotic mice. In vitro sofalcone has a significant bacteriocidal effect against H. pylori and can also significantly prevent adherence of this bacterium to MKN45 cells, thus remarkably reducing IL-8 production of these cells in response to stimulation by H. pylori.. Our results suggest that sofalcone can improve ulcer healing by the mechanisms mentioned above.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cell Adhesion; Chalcone; Chalcones; Disease Models, Animal; Helicobacter Infections; Helicobacter pylori; Humans; Indomethacin; Interleukin-8; Mice; Mice, Inbred BALB C; Stomach Ulcer

We examined the effect of sofalcone, a mucosal protective agent that has been reported to inhibit growth of Helicobacter pylori, on adherence, production of vacuolating toxin (VT), and induction of interleukin-8 (IL-8) secretion by H. pylori. Mixing VT with various concentrations (1.5-100 micrograms/ml) of sofalcone resulted in a 50% decrease in the VT titer. When toxigenic H. pylori strains were incubated in the presence of sofalcone (20 and 40 micrograms/ml), although bacterial growth was not inhibited significantly there was significant inhibition of VT production. Notable inhibition of IL-8 secretion by human gastric cancer cells (MKN 45) was detected in the presence of sofalcone (20-100 micrograms/ml) after co-incubation with H. pylori strains. In flow cytometric analysis, adherence of H. pylori strains to MKN 45 cells was significantly inhibited by treatment with sofalcone (20-60 micrograms/ml), indicating at least one reason for the inhibition of IL-8 secretion. These results show that sofalcone is an effective mucosal protective agent that inhibits both production of VT and induction of IL-8 secretion.

Topics: Anti-Ulcer Agents; Bacterial Adhesion; Bacterial Proteins; Bacterial Toxins; Chalcone; Chalcones; Helicobacter pylori; Humans; Interleukin-8; Tumor Cells, Cultured