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

Stallmach, Andreas; Chan, Chris; Ecker, K. W.; Feifel, G.; Herbst, H.; Schuppan, Detlef; Zeitz, Martin

doi:10.1136/gut.47.3.415

Cited by 94 publications

(73 citation statements)

References 32 publications

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“…The gelatinases A (MMP-2) and B (MMP-9) have been shown to be highly upregulated in small as well as large intestinal inflammation in mice and men [11][12][13][14][15][16]. We have recently reported that selective blockage of gelatinases by the synthetic compound RO28-2653 was effectively ameliorating acute ileitis [17] and colitis [18].…”

Section: Discussionmentioning

confidence: 99%

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The distinct roles of MMP-2 and MMP-9 in acute DSS colitis

Heimesaat¹,

Dunay²,

Fuchs³

et al. 2011

European Journal of Microbiology and Immunology

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Expression of gelatinases A and B, also referred to matrixmetalloproteinases (MMP)-2 and -9, respectively, is increased in inflamed tissues of experimental intestinal inflammation and humans with inflammatory bowel disease (IBDs). Given that we recently reported that treatment with the selective gelatinase inhibitor RO28-2653 ameliorates acute dextrane sulfate sodium (DSS) colitis, we asked whether gelatinase A or B expression is pivotal in mediating large intestinal inflammation. Results from our study reveal that symptoms of acute DSS colitis as well as histopathological colonic changes were ameliorated in MMP-2-, but not MMP-9-deficient mice, and were paralleled by a diminished influx of immune cells. In MMP-2-deficient mice, we observed lower expression of pro-inflammatory cytokines including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-6 in colonic biopsies and less overgrowth of the colonic lumen by potentially pro-inflammatory enterobacteria from the commensal gut microbiota. We conclude that rather MMP-2 than MMP-9 is causative for the establishment of DSS colitis in mice. The discrepancy of these data to prior reports might be due to substantial differences in the intestinal microbiota composition of the mice bred at different animal facilities impacting susceptibility to inflammatory stimuli. Consequently, a detailed survey of the gut microbiota should be implemented in immunological/inflammatory studies in the future in order to allow comparison of data from different facilities.

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Section: Discussionmentioning

confidence: 99%

“…In experimental models of Th1-type inflammation (e.g. rheumatoid arthritis, atherosclerosis and colitis) [7][8][9][10] as well as in humans with inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease [11][12][13][14][15][16], levels of gelatinases A (MMP-2) and B (MMP-9) are increased in inflamed tissue sites.…”

Section: Introductionmentioning

confidence: 99%

The distinct roles of MMP-2 and MMP-9 in acute DSS colitis

Heimesaat¹,

Dunay²,

Fuchs³

et al. 2011

European Journal of Microbiology and Immunology

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“…20 In addition, immunologically mediated cascades that give rise to the release of MMPs seem to play a central role in the pathogenesis of inflammatory bowel diseases. 21 However, while the role of MMPs in Crohn's disease, ulcerative colitis and pouchitis is well established, 16,22,23 less is known about their relevance in CD. By using in situ hybridization, Daum et al 11 were the first to describe the presence of a high number of MMP-1 þ cells in both the subepithelial region and the lamina propria, while MMP-3 þ and TIMP-1 þ cells turned out to be increased only in the subepithelial region of untreated CD.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase pattern in celiac duodenal mucosa

Ciccocioppo

Sabatino

Bauer

et al. 2005

Laboratory Investigation

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Matrix metalloproteinases (MMPs) are a family of endopeptidases playing a key role in tissue remodelling in both physiological and pathological conditions. Since little information is available about their role in celiac disease (CD), our aims were to quantify their expression/activity and to investigate their relation to proinflammatory cytokines in this condition. Duodenal biopsies from untreated, treated celiac patients and controls were used to quantify the expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, MMP-14, their inhibitor TIMP-1, IFN-c and TNF-a by using real-time reverse transcription-polymerase chain reaction and the gelatin/casein/elastin activities by gel zymography, and to isolate lamina propria mononuclear cells (LPMCs). These cells and myofibroblasts isolated from jejunal specimens were incubated in the absence or presence of IFN-c and TNF-a. MMP-1 and MMP-12 mRNA levels were significantly increased in active CD compared to treated (Po0.01 and Po0.0005, respectively) and normal mucosa (Po0.01 and Po0.0005, respectively), and this was paralleled by an upregulation of caseinolytic and elastolytic activities. Furthermore, MMP-12 levels significantly (Po0.05) correlated with those of IFN-c and the degree of villous flattening. MMP-2 turned out to be significantly (Po0.05) reduced in untreated and treated celiacs compared to controls. In active CD, transcripts of TIMP-1 were higher than in treated and controls (Po0.005 and Po0.05, respectively), such as those of IFN-c (Po0.05), whereas TNF-a levels were suppressed (P ¼ 0.0001). In physiological condition, myofibroblasts represent the main source of MMP-2, whereas LPMCs produce almost all MMPs only after cytokine stimulation. Conversely, cells isolated from active patients constitutively express MMPs without any increase after cytokine stimulation, while those from treated patients are in a resting condition. In conclusion, our results show the presence of a peculiar MMP pattern in active CD strongly dominated by MMP-12, correlating either with IFN-c or the degree of mucosal damage.

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“…The role of mucosal MMPs in the differentiation of pouchitis was first examined by Stallmach et al [20]: they revealed that MMP-1 and MMP-2 concentrations in the mucosal biopsy samples were increased in pouchitis compared with uninflamed pouches of patients with UC or familial adenomatous polyposis. Strong MMP-9 and MMP-2 activity was detected in the inflamed pouch being reduced after antibiotic treatment in the study of Ulisse et al [21].…”

Section: Discussionmentioning

confidence: 99%

Faecal matrix metalloprotease-9 is a more sensitive marker for diagnosing pouchitis than faecal calprotectin: results from a pilot study

Farkas

Bálint

Bor

et al. 2014

Expert Review of Gastroenterology & Hepatology

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Background: Potential non-invasive markers of pouchitis would have a great deal of significance within clinical practice. Aim: This study is aimed at assessing the diagnostic accuracy of fecal calprotectin and matrix metalloprotease-9 as potential markers in patients both with and without pouchitis. Patients and methods: Stool and blood samples were collected from 33 ileal pouch-anal anastomosis patients before a follow-up pouchoscopy. Biopsy samples were taken for histological purposes. The presence of cuffitis and stenosis was evaluated with an endoscopy. Calprotectin and matrix metalloprotease-9 were quantified with an enzyme-linked immunosorbent assay. Results: Pouchitis was detected in 30.3% of the patients. The levels of fecal calprotectin and matrix metalloprotease-9 increased significantly in patients with pouchitis. The sensitivity and specificity of matrix metalloprotease-9 was higher than that of fecal calprotectin. Only matrix metalloprotease-9 correlated significantly with the severity of pouchitis. Discussion: Fecal matrix metalloprotease-9 has a high specificity in the diagnosis of pouchitis.KEYWORDS: fecal calprotectin • ileal pouch-anal anastomosis • matrix metalloprotease-9 • pouchitis, ulcerative colitis

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

Abstract: (Gut 2000;47:415-422)

Cited by 94 publications

References 32 publications

The distinct roles of MMP-2 and MMP-9 in acute DSS colitis

The distinct roles of MMP-2 and MMP-9 in acute DSS colitis

Matrix metalloproteinase pattern in celiac duodenal mucosa

Faecal matrix metalloprotease-9 is a more sensitive marker for diagnosing pouchitis than faecal calprotectin: results from a pilot study

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