Table 1: MT expression in IBD patients. CD: Crohn’s disease, UC: ulcerative colitis, IHC: immunohistochemistry, RIA: radio-immunoassay, Ag-hem: Silver-heme saturation assay, and qRT-PCR: quantitative reverse transcriptase-polymerase chain reaction.

StudySubjectsMethodsResults

Clarkson et al. [90]Ileal resection specimens of 13 CD patients (6 had received steroid therapy; 5 had not), 2 UC patients, and 3 controlsIHC on resection specimensLess MT immunoreactivity in patients with IBD than controls; patients on steroid therapy had more immunoreactivity; immunoreactivity in enterocytes and lamina propria

Elmes et al. [91]Ileal resection specimens of 17 CD patients (11 had received steroid therapy; 6 had not), and 5 controlsIHC on resection specimensDecreased intestinal MT in IBD patients; no significant difference when patients had received steroid therapy; immunoreactivity in enterocytes and basement membrane region

Mulder et al. [95]19 ileum and 16 colon specimens from 29 CD patients; 12 colon specimens and 1 ileum specimen from 12 UC patients; colon specimens from 18 control patientsRIA on homogenized mucosa (dissected from resection specimens)MT content was decreased in noninflamed IBD mucosa compared with control mucosa; further decrease, was found in inflamed mucosa; no differences between UC and CD; no significant effect of medication or tissue localization

Sturniolo et al. [96]Colonic biopsies of 24 UC patients and 10 controlsAg-hem on biopsiesReduced MT concentrations in patients with active disease as compared with controls and patients in remission; reduced MT concentrations in inflamed versus noninflamed mucosa taken from the same patient

Bruwer et al. [87]22 CD patients, 48 UC patients, 10 controlsIHC on resection specimensMT overexpression in the fibroblasts of all ulcerative and/or fissural lesions in UC and CD; MT overexpression in intestinal epithelial cells of 40% of UC and CD lesions correlated significantly with the grade of inflammation

Lawrance et al. [89]Colonic resection specimens with moderately severe histological inflammation from 12 UC and 6 CD patients (with moderately severe clinical disease) and from 6 controlsDNA microarrayDecrease of MT1H and MT1G mRNA expression in UC; no difference in CD

Ioachim et al. [92]Ileum, colon or rectum resection specimens from 10 CD patients, 41 UC patients, 5 controlsIHCDecreased MT expression in UC and CD compared with normal mucosa; no difference in MT expression between UC and CD; in UC, a gradually decreased expression from remission, to resolving and to active phase was observed; only epithelial MT expression

Kruidenier et al. [93]Resection specimens from 19 CD patients, 15 UC patients, 18 controlsRIA on tissue homogenates and IHC on resection specimensRIA: Lower tissue MT content in inflamed CD and UC mucosa compared with noninflamed and control mucosa; IHC: decreased MT-positive epithelial cell numbers at inflamed sites in CD and UC patients; no detection of MT in lamina propria

Dooley et al. [88]2 sets of colon samples: (a) control (1 uninvolved colon from CD patient), 1 CD patient, and 1 UC patient; (b) control, 1 azathioprine-treated CD patient, and 1 azathioprine-treated UC patient; drug-treated CaCo-2 cellsmicroarray and qRT-PCR with consensus primer sequences for multiple metallothionein genes.Microarray: upregulation of MT1F, MT1G, MT1H in CD in tissue set (a); downregulation of MT1F, MT1H, MT1L in azathioprine-treated CaCo-2 cells; confirmed by qRT-PCR