Benzoxazole derivative B-98 ameliorates dextran sulfate sodium-induced acute murine colitis and the change of T cell profiles in acute murine colitis model

Abstract

BACKGROUND/AIMS: The unique role of enzyme 5-lipoxygenase (5-LO) in the production of leukotrienes makes it a therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to evaluate the effects of B-98, a newly synthesized benzoxazole derivatives and a novel 5-LO inhibitor, in a mouse model of IBD induced by dextran sulfate sodium (DSS). METHODS: C57BL/6 mice were randomly assigned to four groups: normal control, DSS colitis (DSS+saline), low dose B-98 (DSS＋B-98 20 mg/kg) and high dose B-98 (DSS＋B-98 100 mg/kg). B-98 was administered with 3% DSS intraperitoneally. The severity of the colitis was assessed via the disease activity index (DAI), colon length, and histopathologic grading. The production of inflammatory cytokines interleukin (IL)-6 was determined by RT-PCR. Th cells were examined for the proportion of Th1 cell, Th2 cell, Th9 cell, Th17 cell and Treg cell using intracellular cytometry. RESULTS: The B-98 group showed lower DAI, less shortening of the colon length and lower histopathologic grading compared with the DSS colitis group (p<0.01). The expression of IL-6 in colonic tissue was significantly lower in the B-98 groups than the DSS colitis group (p<0.05). The cellular profiles revealed that the Th1, Th9 and Th17 cells were increased in the DSS colitis group compared to the B-98 group (p<0.05). CONCLUSIONS: Our results suggest that acute intestinal inflammation is reduced in the group treated with B-98 by Th1, Th9 and Th17 involved cellular immunity.