Biol. Pharm. Bull. 29(10) 2041—2045 (2006)

characterized by frequent relapses or remissions of inflammation in the colonic mucosa. It has been reported that spontaneous colitis, which consistently develops in knockout and transgenic murine models, does not occur when these mice are maintained in germ free conditions, and suggested the involvement of bacteria in disease development. Recently, it has been shown that Fusobacterium varium were identified in the mucosa of a significant number of patients with UC, and specific antibody against F. varium was detected in the sera from patients with UC. It has also been reported that F. varium culture supernatants contained high concentrations of butyrate, and the enema containing either butyric acid or F. varium culture supernatants caused UC-like lesions in mice. However, the role of butyrate on the pathogenesis of UC has not been fully elucidated. Butyrate produced in the colonic lumen by anaerobic microbial fermentation of undigested carbohydrates, has been shown to induce proliferation, differentiation, cell cycle arrest, and apoptosis in colonic epithelial cells. In spite of many studies, the effect of butyrate on colonic epithelial cells is not fully understood. A major limitation to studying the effect of butyrate using primary cultured colonic epitherial cells is the difficulty in maintaining viability of the cells after isolation. Therefore, most studies have been employed using colonic cancer cells. These cell lines have proven useful in analyzing function of colonic epithelial cells. However, butyrate has often been observed to exert paradoxical effects. The results have varied according to the cell line used, and because of their malignant phenotype, their properties and functions may not be representative of colonic epithelial cells in vivo. The mouse colonic epithelial cell line, MCE301, has been established from a primary culture of gastric mucosal cells of transgenic mice harboring a temperature-sensitive simian virus 40 (tsSV40) large T-antigen gene. The cells were not transformed, as judged by the absence of anchorage-independent growth in soft agar and lack of tumor formation in nude mice. Because MCE301 cells have been shown to retain many of the characteristics of normal colonic epithelial cells, the studies using MCE301 cells provide useful information to understand various aspect of colonic epithelial cell function and cellular response to various stimuli. Recent findings have suggested that butyrate produced by anaerobic intestinal bacteria might contribute to the formation of UC-like lesions. In the present study, the effect of butyrate on cell viability of colonic epithelial cells was examined using MCE301 cells in vitro, and it was found that butyrate induced necrotic cell death in MCE301 cells. Results of this study support that the necrotic cell death of MCE301 cells induced by butyrate may be useful as a novel in vitro model of UC to screen useful drugs for the treatment of the disease.