Abstract
BackgroundTissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC).MethodsTIMP-1, TIMP-2 and TIMP-4 serum levels were determined in 53 patients with ulcerative colitis (UC), 52 patients with Crohn's disease (CD) and 50 HC, by means of commercially available enzyme-linked immunosorbent assays. The levels of TIMPs were evaluated with regard to the levels of inflammatory markers, such as C reactive protein (CRP) and serum amyloid A (SAA) and the clinical characteristics of patients, so that potential correlations could be recorded.ResultsMean serum TIMP-1 levels were 414.9 ± 17.6 ng/mL in UC patients, 446.1 ± 22.8 ng/mL in CD patients and 296.5 ± 20.6 ng/mL in HC. UC and CD patients had significantly higher serum TIMP-1 levels when compared to HC, (p < 0.0001 in both groups). Mean serum TIMP-1 levels were significantly higher in patients with active IBD (450.5 ng/mL) in comparison with patients with inactive disease (417.3 ng/mL, p = 0.03). Moreover, males showed significantly higher mean serum TIMP-1 levels (399.8 ng/mL), compared to females (368.5 ng/mL, p = 0.04). Mean serum TIMP-2 levels did not differ between UC and CD patients or HC (p > 0.05 in all cases). Mean serum TIMP-4 levels were 1761.2 ± 67.7 pg/mL in UC patients, 1708.1 ± 73.4 pg/mL in CD patients and 5573.4 ± 1246.3 pg/mL in HC. UC and CD patients had significantly lower serum TIMP-4 levels when compared to HC (p = 0.008 and p = 0.02 respectively). Mean serum TIMP-4 levels were significantly lower in males (2772.9 pg/mL), compared to females (3299.0 pg/mL, p = 0.01). In addition, CRP levels showed a statistically significant correlation with TIMP-1 (r = 0.247, p = 0.01), and TIMP-4 levels (r = 0.217, p = 0.03). Similarly, there was a statistically significant correlation between SAA levels and both TIMP-1 (r = 0.264, p = 0.008) and TIMP-4 serum levels (r = 0.212, p = 0.03).ConclusionAn imbalance between TIMP-1 and TIMP-4 serum levels is present in IBD patients. TIMP-1 levels could be used not only for diagnostic purposes but also for the assessment of activity in IBD. Gender tends to influence TIMP-1 and TIMP-4 serum levels. These new findings bring into question the potential role of TIMPs in IBD, thus underlining the need for future studies which could offer new insight into this matter.
Highlights
Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling
ulcerative colitis (UC) and Crohn's disease (CD) patients had significantly higher serum TIMP-1 levels compared to healthy controls (HC) (p < 0.0001 in both groups)
The mean serum TIMP-1 levels were significantly higher in patients with active inflammatory bowel disease (IBD) (450.5 ng/mL) as compared with patients with inactive disease
Summary
Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC). The inflammatory cell infiltrate observed in chronic mucosal inflammation is associated with changes in epithelial proliferation and migration and accompanied by intensive remodeling of the subepithelial connective tissue, which in turn leads to increased turnover of extracellular matrix (ECM) components [1,2]. Like MMPs, the expression of TIMPs in the tissue is controlled to maintain a balance in the metabolism of the ECM [4]. Disruption of this balance may result in a number of pathogenic processes. Numerous studies have indicated that, independently of MMP inhibition, TIMPs are multifunctional proteins involved in tissue remodeling and wound healing and in many other physiological and pathological processes such as angiogenesis, steroidogenesis, hematopoiesis, cell growth and cell survival [4]
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