title: Possible involvement of neutrophil elastase in impaired mucosal repair in patients with ulcerative colitis.
abstract: BACKGROUND
  Little information is available on the relative contribution of peptide growth factors and leukocyte-derived proteinases to the repair processes in inflammatory bowel disease (IBD). We investigated their possible roles in epithelial cell restitution and proliferation in patients with IBD.
  
  
  METHODS
  The expression of hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), transforming growth factor-beta (TGF-beta), and neutrophil elastase (NE) was examined in colonic mucosal tissues. The effects of organ culture supernatants of mucosal tissues on epithelial cell restitution and proliferation were analyzed in vitro using an intestinal cell line, IEC-6 cells.
  
  
  RESULTS
  Most organ cultures detected the presence of measurable levels of HGF, with a relative paucity of KGF and TGF-beta activity. Greater levels of HGF were obtained in the mucosa involved with IBD, especially in patients with ulcerative colitis (UC). The mucosa involved with UC also showed higher amounts of NE. The supernatants from the mucosa involved with UC possessed a prominent stimulatory effect on the restitution of IEC-6 cells. By contrast, significant suppression beyond baseline levels was observed for the proliferation of IEC-6 cells when they were incubated with recombinant HGF plus the supernatants from the mucosa involved with UC. This suppression was diminished considerably by preincubation of the supernatants with the anti-NE antibody.
  
  
  CONCLUSIONS
  HGF produced in the intestinal mucosa may be an important stimulator acting on epithelial cell restitution in patients with IBD. However, NE released in situ may impair mucosal repair through inhibiting epithelial cell proliferation in patients with UC.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuno
authors.forename: Kenji
authors.initials: K
authors.lastname: Ina
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nishiwaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shimada
authors.forename: Akira
authors.initials: A
authors.lastname: Imada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishio
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nobata
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.forename: Kenji
authors.initials: K
authors.lastname: Hibi
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kusugami
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000473:pathology*; D004847:Epithelial Cells; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology*; D019272:Leukocyte Elastase / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D011336:Probability; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D019272:Leukocyte Elastase