Kallikrein-kinin system in inflammatory bowel diseases: Intestinal involvement and correlation with the degree of tissue inflammation

M. Devani, M. Vecchi, S. Ferrero, E. Contessini Avesani, C. Arizzi, L. Chao, R. W. Colman, M. Cugno

Research output: Contribution to journalArticle

Abstract

Background.: Tissue kallikrein and its natural inhibitor, kallistatin, play opposite roles in the generation of bradykinin, a potent mediator of inflammation. Observations on experimental models and humans with ulcerative colitis suggest a pathogenetic role of the kallikrein-kinin system in inflammatory bowel diseases. Aim.: To evaluate tissue kallikrein and kallistatin in intestinal tissue samples from Crohn's disease and ulcerative colitis patients with different degrees of disease involvement. Patients and methods.: Full-thickness surgical intestinal samples were obtained from 144 subjects (38 normal controls, 32 inflammatory controls, 38 Crohn's disease, 36 ulcerative colitis) and tested for kallikrein and kallistatin by immunoperoxidase techniques. Results.: Compared with controls, kallikrein immunoreactivity was significantly weaker in goblet cells (p = 0.0001) and significantly stronger in interstitium (p = 0.0001) of the Crohn's disease and ulcerative colitis samples. Kallistatin colocalised with kallikrein, with almost no reactivity in goblet cells but strong reactivity in interstitium of inflammatory bowel disease patients (p = 0.0001 versus controls). The kallikrein and kallistatin depletion of goblet cells and the increased interstitial kallikrein and kallistatin reactivity correlated with the degree of tissue inflammation (p = 0.0001). Disease-free samples had normal kallikrein and kallistatin patterns. Conclusions.: Kallikrein-kinin system is actively involved in inflammatory bowel disease as a result of the release of kallikrein in the intestinal extracellular space; this involvement correlates with the degree of tissue inflammation. The normal pattern observed in the disease-free samples seems to rule out a genetic defect of kallikrein and kallistatin in inflammatory bowel diseases.

Original languageEnglish
Pages (from-to)665-673
Number of pages9
JournalDigestive and Liver Disease
Volume37
Issue number9
DOIs
Publication statusPublished - Sep 2005

Keywords

  • Crohn's disease
  • Intestinal tissue kallikrein
  • Kallistatin
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

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