Macrolide antibiotics are believed to inhibit mucus secretion but the mechanism of action is unclear. This study was designed to investigate an effect of roxithromycin on MUC2 gene expression in cultured intestinal epithelial cells (HM3-MUC2 cells). A reporter gene assay was used for analysis. Roxithromycin suppressed MUC2 gene transcriptional activity in a dose-dependent manner in HM3-MUC2 cells. Phorbol 12-myristate 13-acetate (PMA), lipoteichoic acid (LTA), lipopolysaccharide (LPS) and leukotriene D4 (LTD4) significantly increased MUC2 luciferase activities in the following order: PMA > LTA > LTD4 > LPS. Roxithromycin also decreased MUC2 gene transcriptional activity induced by PMA in a dose-dependent manner. NF-ĸB activation, but not AP-1 activation, was significantly suppressed by roxithromycin in HM3-MUC2 cells. A suppression of NF-ĸB activation was also observed in NCI-H292 cells. These results suggest that roxithromycin suppresses MUC2 gene expression in epithelial cells and that this suppression is probably via inhibition of NF-ĸB activation.

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