Increased intestinal expression of heme oxygenase-1 and its localization in patients with ulcerative colitis

Heme oxygenase-1 (HO-1) is regarded as a sensitive and reliable indicator of cellular oxidative stress. Two end products of heme degradation, carbon monoxide (CO) and bilirubin, are involved in the protective role of HO-1 against oxidative injury. We have demonstrated enhanced expression of this enzyme and increased concentration of CO in experimental models of colitis, but the role of HO-1 in patients with ulcerative colitis (UC) has not been extensively investigated. The aim of the present study was to determine the intestinal levels and localization of ho-1 mRNA and HO-1 protein in patients with UC. Eighteen patients with UC and 13 patients with colon cancer were prospectively selected from subjects who underwent colonoscopy. Biopsy specimens were obtained from the inflamed mucosa of UC patients and from the normal mucosa at least 5 cm from the margin of carcinoma. The expression of ho-1 mRNA was assayed by real-time polymerase chain reaction (PCR). The colonic expression of HO-1 was determined by immunohistochemistry and western blotting using a monoclonal antibody against HO-1. The expression of ho-1 mRNA and HO-1 protein was significantly increased in the colonic mucosa of patients with active UC compared with normal mucosa. In the patients with active UC, mononuclear cells in the submucosa of the colon were positive for HO-1, and there was negligible staining in the epithelial cells. The present findings are evidence of the induction of HO-1 in the colon of UC patients.