Benzoxazole Derivative B-98 Ameliorates Dextran Sulfate Sodium-induced Acute Murine Colitis and the Change of T Cell Profiles in Acute Murine Colitis Model.
- Author:
Eun Mi SONG
1
;
Sung Ae JUNG
;
Jong Soo LEE
;
Seung Eun KIM
;
Ki Nam SHIM
;
Hye Kyung JUNG
;
Kwon YOO
;
Hae Young PARK
Author Information
- Publication Type:Original Article ; English Abstract
- Keywords: 5-Lipoxygenase inhibitors; Inflammatory bowel diseases; Colitis
- MeSH: Acute Disease; Animals; Arachidonate 5-Lipoxygenase/chemistry/metabolism; Benzoxazoles/chemistry/*pharmacology; Colitis/chemically induced/pathology/*prevention & control; Colon/drug effects/pathology/physiology; Dextran Sulfate/toxicity; Disease Models, Animal; Forkhead Transcription Factors/metabolism; Injections, Intraperitoneal; Interleukin-6/genetics/metabolism; Lipoxygenase Inhibitors/chemistry/*pharmacology; Male; Mice; Mice, Inbred C57BL; Severity of Illness Index; T-Lymphocytes/classification/*drug effects/metabolism
- From:The Korean Journal of Gastroenterology 2013;62(1):33-41
- CountryRepublic of Korea
- Language:Korean
- 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.
