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 H(2)O(2) to measure cell viability. The expression of NE was determined in YAMC cells treated with H(2)O(2). NE-silenced YAMC cells were also treated with H(2)O(2) 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 H(2)O(2). H(2)O(2) treatment significantly induced NE in YAMC cells, and NE-silenced YAMC cells were also resistant against the treatment of H(2)O(2). 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.