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Comparable expression of matrix metalloproteinases 1 and 2 in pouchitis and ulcerative colitis

Abstract

BACKGROUND AND AIMS Matrix metalloproteinases (MMPs) are implicated in the tissue destruction associated with inflammatory diseases. Proctocolectomy with ileo-anal pouch (IAP) anastomosis is associated with pouchitis, particularly in patients with ulcerative colitis (UC). The aim of this study was to quantify MMP-1 and MMP-2 in inflamed and uninflamed pouches of patients with UC compared with those with active UC. IAP patients with familial adenomatous polyposis (FAP) served as controls.

METHODS Biopsies were taken from 33 patients with IAP (UC, n=25; FAP, n=8) and from 10 UC patients. MMP-1 and MMP-2 were quantified using sandwich enzyme linked immunosorbent assays. In addition, northern and western blotting and in situ hybridisation experiments were performed.

RESULTS In pouchitis (n=11), MMP-1 and MMP-2 concentrations were increased compared with uninflamed pouches of patients with UC (n=14) or FAP (n=8) (MMP-1 17.7 ng/mg protein v 7.8 (UC)v 7.6 (FAP), p⩽0.05; MMP-2 16.4v 9.5 (UC) v 6.3 (FAP), p⩽0.05). Western and northern blots revealed increased MMP-1 and MMP-2 protein and transcript concentrations in inflamed pouches. Mesenchymal cells were identified as major producers of MMP-1 and MMP-2 in pouchitis. A similar increase in MMPs was observed in tissues of patients with active UC.

CONCLUSIONS Our results support the hypothesis that MMPs are involved in mucosal destruction and crypt hyperplasia, as seen in pouchitis.

  • ileo-anal pouch
  • matrix metalloproteinases
  • pouchitis
  • Abbreviations used in this paper

    IAP
    ileo-anal pouch
    MMPs
    matrix metalloproteinases
    UC
    ulcerative colitis
    FAP
    familial adenomatous polyposis
    ECM
    extracellular matrix
    TIMPs
    tissue inhibitors of metalloproteinases
    PDAI
    pouchitis disease activity index
    IL
    interleukin
    TNF-α
    tumour necrosis factor α
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  • Abbreviations used in this paper

    IAP
    ileo-anal pouch
    MMPs
    matrix metalloproteinases
    UC
    ulcerative colitis
    FAP
    familial adenomatous polyposis
    ECM
    extracellular matrix
    TIMPs
    tissue inhibitors of metalloproteinases
    PDAI
    pouchitis disease activity index
    IL
    interleukin
    TNF-α
    tumour necrosis factor α
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