title: Serpin B1 protects colonic epithelial cell via blockage of neutrophil elastase activity and its expression is enhanced in patients with ulcerative colitis.
abstract: 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.
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hirai
authors.forename: Natsuko
authors.initials: N
authors.lastname: Hayashi
authors.forename: Akihito
authors.initials: A
authors.lastname: Harusato
authors.forename: Ken
authors.initials: K
authors.lastname: Inoue
authors.forename: Kohei
authors.initials: K
authors.lastname: Fukumoto
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yagi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008875:Middle Aged; D015843:Serpins / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: C522950:Serpinb1a protein, mouse; D015843:Serpins; C075177:SERPINB1 protein, human; D006861:Hydrogen Peroxide; D019272:Leukocyte Elastase