Background and aims-Matrix metalloproteinases (MMPs) are implicated in the
tissue destruction associated with inflammatory diseases. Proctocolectomy w
ith ileo-anal pouch (IAP) anastomosis is associated with pouchitis, particu
larly in patients with ulcerative colitis (UC). The aim of this study was t
o quantify MMP-1 and MMP-2 in inflamed and uninflamed pouches of patients w
ith UC compared with those with active UC. IAP patients with familial adeno
matous 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 enz
yme 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) (M
MP-1 17.7 ng/mg protein v 7.8 (UC) v 7.6 (FAP), p less than or equal to 0.0
5; MMP-2 16.4 v 9.5 (UC) v 6.3 (FAP), p less than or equal to 0.05). Wester
n and northern blots revealed increased MMP-1 and MMP-2 protein and transcr
ipt concentrations in inflamed pouches. Mesenchymal cells were identified a
s major producers of MMP-1 and MMP-2 in pouchitis. A similar increase in MM
Ps was observed in tissues of patients with active UC.
Conclusions-Our results support the hypothesis that MMPs are involved in mu
cosal destruction and crypt hyperplasia, as seen in pouchitis.