Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 as biomarkers of ulcerative colitis activity

Abstract

AIM:Overexpression of mucosal metalloproteinases (MMP) have been demonstrated recently in inflammatory bowel disease. Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases (TIMP). The aim of this study was to evaluate the effect of ulcerative colitis (UC) on MMP-1 and TIMP-1 plasma concentrations, as two possible biomarkers of the disease activity. METHODS:MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS:Plasma concentrations of both MMP-1 (13.7±0.2 ng/ml) and TIMP-1 (799±140 ng/ml) were significantly elevated in UC patients in comparison to healthy controls (11.9±0.9 ng/ml and 220±7 ng/ml respectively). There was no correlation between TIMP-1 and MMP-1 concentrations (r=-0.02). TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration. There was no correlation between MMP-1 and laboratory, clinical or endoscopic indices of the disease activity. CONCLUSION:These results confirm the role of both MMP-1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.Wiercinska-Drapalo A, Jaroszewicz J, Flisiak R, Prokopowicz D. Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 as biomarkers of ulcerative colitis activity.

Increased Protein Expression of Matrix Metalloproteinases -1, -3, and -9 and TIMP-1 in Patients with Gluten-Sensitive Enteropathy

“…In inflammatory bowel disease tissue, both mRNA transcripts and protein levels of this inhibitor were increased [13,19]. Raised levels of soluble TIMP-1 have been found in culture supernatants of inflamed biopsies from ulcerative colitis and Crohn`s disease patients [32,33]. Increased soluble TIMP-1 levels were found in synovial fluid [27] and serum samples of rheumatoid arthritis patients [28].…”

Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection

“…In experimental colitis, MIF expression was increased during colitis and the severity of colitis was reduced by anti-MIF antibody [68], which suppressed T-helper 1-type cytokines and matrix metalloproteinase (MMP). It has been reported that MMP is overexpressed in infl ammatory bowel disease (IBD) and in experimental colitis [69]. Moreover, MIF-defi cient mice showed mild infl ammation compared with wild-type mice [70].…”

Matrix metalloproteinases in inflammatory bowel disease: Boon or a bane?

“…116,117 TIMP-1 levels also inversely correlated with scored endoscopic degree of mucosal injury, disease activity index, and clinical activity index values in patients with UC. 118 In IBD, TIMP-3 is expressed around blood vessels, within the macrophage-rich area, below the neutrophilic infiltrate of the ulcer bed, and in the lamina propria surrounding damaged crypts. 16 The ratio between MMP-1/TIMP-1 and MMP-3/TIMP-1 is increased in inflamed colon of IBD patients compared with noninflamed tissue samples, whereas TIMP-2 mRNA remained unaltered.…”