Search

RT-PCR. IuB phosphorylation/degradation and intranuclear translocation of nuclear factor kappaB (NF-uB) were evaluated by Western blot analysis. The molecular marker of endoplasmic reticulum (ER) stress, including p-JNK, p-eIF2a, CHOP, and XBP1 was evaluated using western blotting and PCR. In the dextran sulfate sodium (DSS) colitis model, mice were given 4% DSS for 5 days with or without roxithromycin. Using the extracted colon tissue, immunohistochemical staining for phospho-IuB kinase (IKK) antibody was performed. Results: Roxithromycin significantly inhibited the upregulated expression of IL-8 in HCT116 cells stimulated with TNF-a. Pretreatment with roxithromycin attenuated IuB phsophorylation/ degradation and NF-uB nuclear translocation. CHOP and XBP1 mRNA expression was enhanced in the presence of TNF-a, and it was dampened by pretreatment of roxithromycin. JNK phosphorylation and the level of p-eIF2a was also downregulated by the pretreatment of roxithromycin. Administration of roxithromycin significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phosphoIKK activation was significantly decreased in roxithromycinpretreated mice. Conclusions: These results indicate that roxithromycin inhibits NF-uB activation and ER stress in intestinal epithelial cells and that it ameliorates experimental murine colitis. These results suggest that roxithromycin is a potential therapeutic agent for the treatment of inflammatory bowel disease.