Reactive Oxygen Species and Colonic Epithelial Cell Apoptosis in Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is one of the inflammatory bowel diseases of unknown etiology characterized by its localization to the large intestine. According to pathological examination, which reveals mucosal inflammatory cell infiltration, goblet cell depletion, and distortion of crypt architecture, it is clear that the target of this disease is epithelial cells. Some reports note that epithelial cell damage is mediated by apoptotic cell death. The aim of this study was to elucidate the role of reactive oxygen species (ROS) in the induction of colonic epithelial cell apoptosis. Colonie biopsies from active and inactive lesions of UC patients and from normal tissues of patients with colon polyps were used. ROS production from the colonic tissues were measured using a chemiluminescence assay. Apoptotic cells were detected by the TUNEL technique. Superoxide dismutase (SOD), Fas, and Bcl-2 were detected by immunohistochemistry. ROS production was increased in active UC compared with inactive UC or normal mucosa. SOD was strongly expressed in the epithelial cells of active UC compared with inactive UC mucosa. The extent of TUNEL-positive epithelial cells was more extensive in active UC compared with inactive UC or nomal mucosa. There was a positive correlation between ROS production and the extent of TUNEL-positive cells. There was a tendency for Fas-positive cells to be fewer in active and inactive UC compared with normal mucosa, but there was no clear tendency for Bcl-2-positive cells. Based on these results, ROS rather than the Fas/Fas ligand system is suggested to have an important role in inducing epithelial cell apoptosis in UC.