Possible involvement of neutrophil elastase in impaired mucosal repair in patients with ulcerative colitis.
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.
Kuno
Yuji
Y
First Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Ina
Kenji
K
Nishiwaki
Tsuyoshi
T
Tsuzuki
Tomoyuki
T
Shimada
Masaaki
M
Imada
Akira
A
Nishio
Yuji
Y
Nobata
Kazuo
K
Suzuki
Takefumi
T
Ando
Takafumi
T
Hibi
Kenji
K
Nakao
Akimasa
A
Yokoyama
Tadashi
T
Yokoyama
Yasuhisa
Y
Kusugami
Kazuo
K
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
D015415:Biomarkers; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D019272:Leukocyte Elastase