Butyrate induces necrotic cell death in murine colonic epithelial cell MCE301

Abstract

Recent findings have suggested that organic acids produced by anaerobic intestinal bacteria might contribute to the pathogenesis of colonic ulcers. In this study, it was shown that butyrate caused potent cytotoxicity in the murine normal colonic epithelial cells MCE301 at physiological concentrations. Several markers of apoptosis, such as phosphatidyl serine externalization, cytochrome c release, DNA fragmentation, and chromatin condensation were negative after butyrate exposure. Inhibitor of caspases failed to protect against butyrate cytotoxicity. By transmission electron microscopy, marked swollen mitochondria and vacuolization within the cytoplasm was observed by treatment of butyrate. Collective, these data indicated that butyrate-induced cell death caused through a necrosis-like process. Butyrate induced cell death was reduced partially by treatment with prednisolone or 5-aminosalicylates in a concentration dependent manner. These results suggest that (1) butyrate induces necrotic cell death but not apoptotic cell death, and (2) the necrotic cell death induced by butyrate may be useful as a novel in vitro model of ulcerative colitis to screen useful drugs for the treatment of the disease. © 2006 Pharmaceutical Society of Japan.