Serpin B1 protects colonic epithelial cell via blockage of neutrophil elastase activity and its expression is enhanced in patients with ulcerative colitis

Uchiyama K, Naito Y, Takagi T, Mizushima K, Hirai Y, Hayashi N, Harusato A, Inoue K, Fukumoto K, Yamada S, Handa O, Ishikawa T, Yagi N, Kokura S, Yoshikawa T. Serpin B1 protects colonic epithelial cell via blockage of neutrophil elastase activity and its expression is enhanced in patients with ulcerative colitis. Am J Physiol Gastrointest Liver Physiol 302: G1163-G1170, 2012. First published March 15, 2012; doi:10.1152/ajpgi.00292.2011.-Serpin B1 is a monocyte neutrophil elastase (NE) inhibitor and is one of the most efficient inhibitors of NE. In the present study, we investigated the role of serpin B1 in the pathogenesis of ulcerative colitis by using clinical samples and an experimental model. The colonic expression of serpin B1 was determined by real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistological studies in both normal and inflamed mucosa from patients with ulcerative colitis. Serpin B1 mRNA expression was determined by real-time PCR in the mouse dextran sodium sulfate (DSS)-induced colitis model. Young adult mouse colonic epithelial (YAMC) cells were used to determine the role of serpin B1. Serpin B1 gene transfected YAMC cells were treated with H2O2 to measure cell viability. The expression of NE was determined in YAMC cells treated with H2O2. NE-silenced YAMC cells were also treated with H2O2 and then measured for viability. Upregulated expression of serpin B1 in colonic mucosa was confirmed from patients with active ulcerative colitis. Immunohistochemical studies showed that serpin B1 expression was localized not only in inflammatory infiltration cells but also in epithelial cells. Serpin B1 mRNA expression was also increased in colonic mucosa of mouse DSS-induced colitis. Serpin B1-transfected YAMC cells were resistant against the treatment of H2O2. H2O2 treatment significantly induced NE in YAMC cells, and NE-silenced YAMC cells were also resistant against the treatment of H2O2. These results suggest that serpin B1 may be a novel marker of active ulcerative colitis and may play an important role in the pathogenesis of inflammatory bowel disease.