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Possible involvement of neutrophil elastase in impaired mucosal repair in patients with ulcerative colitis

  • Positioning of treatment for IBD by repairing mucosa
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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-β (TGF-β), 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-β 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.

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Authors and Affiliations

  1. First Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Yuji Kuno, Kenji Ina, Tsuyoshi Nishiwaki, Tomoyuki Tsuzuki, Masaaki Shimada, Akira Imada, Yuji Nishio, Kazuo Nobata, Takefumi Suzuki, Takafumi Ando & Kazuo Kusugami

  2. Second Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan

    Kenji Hibi & Akimasa Nakao

  3. Yokoyama Gastrointestinal Hospital, Nagoya, Japan

    Tadashi Yokoyama & Yasuhisa Yokoyama

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  1. Yuji Kuno
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  2. Kenji Ina
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  3. Tsuyoshi Nishiwaki
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  4. Tomoyuki Tsuzuki
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  5. Masaaki Shimada
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  6. Akira Imada
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  7. Yuji Nishio
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  8. Kazuo Nobata
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  9. Takefumi Suzuki
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  10. Takafumi Ando
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  11. Kenji Hibi
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  14. Yasuhisa Yokoyama
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  15. Kazuo Kusugami
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Kuno, Y., Ina, K., Nishiwaki, T. et al. Possible involvement of neutrophil elastase in impaired mucosal repair in patients with ulcerative colitis. J Gastroenterol 37 (Suppl 14), 22–32 (2002). https://doi.org/10.1007/BF03326409

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  • DOI: https://doi.org/10.1007/BF03326409

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