Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

Santana, Alfredo; Medina, Carlos; Paz-Cabrera, María Cristina; Dı́az-González, Federico; Farre, Esther; Salas, Antonio; Radomski, Marek W.; Quintero, Enrique

doi:10.3748/wjg.v12.i40.6464

Cited by 85 publications

(97 citation statements)

References 39 publications

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“…Attenuation of the DSS-induced colitis in MMP-9-deficient mice has been reported previously (44). To validate these findings, we compared the induction of experimental colitis in WT and MMP-9 Ϫ/Ϫ mice; we found that the severity of experimental colitis after 7 days of oral administration of 3% DSS was significantly lower in MMP-9 Ϫ/Ϫ mice compared with the WT mice.…”

Section: Dss-induced Epithelial Permeability Is Attenuated In Mmp-9supporting

confidence: 71%

“…MMP-9 levels in colonic tissue were found to be elevated in a rat models of chemically induced dextran sodium sulfate (DSS) colitis and treatment with a synthetic inhibitor of MMPs (CGS-27023-A) attenuated the DSS-induced colitis (30,31). Furthermore, the DSS and TNBS colitis as well as Salmonella typhimurium-induced enterocolitis were attenuated in MMP-9 Ϫ/Ϫ mice (13,35,44). In a double knockout study, MMP-9 has been shown to have overriding effect on the protective role of MMP-2 in mediating tissue damage during experimental colitis (13).…”

mentioning

confidence: 99%

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Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

Nighot

Al–Sadi

Rawat

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

107

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Section: Dss-induced Epithelial Permeability Is Attenuated In Mmp-9supporting

confidence: 71%

mentioning

confidence: 99%

Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

Nighot

Al–Sadi

Rawat

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

107

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“…For instance, the sex of the host is known to be correlated to differences in the immune responses of males and females to inflammatory stimuli [38][39][40]. According to our experiences (Prof. Britta Siegmund, Charité Berlin; personal communication) male mice (as used in [35]) might be more resistant to colitis induction by DSS as compared to female animals (in our study) whereas mice younger than 8 weeks of age (as used in [36]) are more susceptible to acute DSS colitis as compared to 3-month-old animals (in the presented study). Furthermore, the important role of the host microbiota composition in initiating, mediating, and perpetuating acute and chronic intestinal inflammation in mice and men is of current debate and highlighted by a plethora of recent studies [41][42][43][44][45][46][47].…”

Section: Discussionsupporting

confidence: 50%

“…MMP-9-deficient mice were shown to be protected from acute colitis induced either by DSS [34,35] or by Salmonella Typhimurium [34]. Studies with bone marrow chimera revealed that MMP-2 and MMP-9 derived from epithelial but not immune cells, mediated colonic inflammation [34,36].…”

Section: Discussionmentioning

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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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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“…The studies published so far have confirmed the overexpression of MMPs, including MMP-3 and -9, both in ulcerative colitis and in Crohn's disease (CD). Alterations of MMPs activity depending on the degree of disease exacerbation have been observed in animal models with induced bowel inflammation [11,12]. Elevated concentrations of MMPs have also been noted in biopsy specimens collected from inflamed fragments of the alimentary tract [1,2,13,14].…”

Section: Discussionmentioning

confidence: 99%

Metalloproteinase-3 and -9 as Novel Markers in the Evaluation of Ulcerative Colitis Activity in Children

Kofla-Dłubacz¹,

Matusiewicz²,

Krzesiek³

et al. 2014

Adv Clin Exp Med

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Objectives. The enhanced activity of matrix endopeptidases (MMPs) involved in the degradation of connective tissue has been noted in tissue samples from the digestive tract in inflammatory bowel disease (IBD), however sera concentrations of MMPs, a potential tool for diagnostic tests in IBD patients, have not been established so far. The goal of the studies was to evaluate the concentrations of MMP-3 and MMP-9, in the sera of children suffering from ulcerative colitis (UC) in relation to disease activity. Material and Methods. The study was comprised of 31 children with UC (aged 3-18 years) and 37 children in the control group (aged 1-18 years). Disease activity was estimated using the Truelove-Witts scale. MMP-3 and -9 concentrations were determined using ELISA tests. Results. Median MMP-3 concentrations were 18.4 ng/mL (95% CI: 12.5-24.3) for moderate and severe, 4.35 ng/mL (95% CI: 2.5-7.8) for the mild form of UC and 1.8 ng/mL (95% CI: 1.2-2.5) for the control group. Median MMP-9 concentrations were 18.0 ng/mL (95% CI: 2.83-36.6) for moderate and severe, 1.55 ng/mL (95% CI: 0.4-3.0) for the mild form of UC and 1.3 ng/mL (95% CI: 0.7-1.96) for the control group. Serum MMP-3 and MMP-9 concentrations in the moderate group were higher than those in the mild and control groups (p < 0.001). MMP-3 concentrations in the mild group also differed from those in the control group (p < 0.001). Among the parameters studied (MMP-3, MMP-9, CRP and ESR), MMP-3 had the highest discriminative value (AUC = 0.9, p < 0.001, sensitivity = 71%, specificity = 92%) in distinguishing patients with UC from healthy individuals. Conclusions. Elevation of MMP-3 and MMP-9 concentrations along with the disease activity suggests the possibility of their application in the evaluation of the clinical activity of UC (Adv Clin Exp Med 2014, 23, 1, 103-110).

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Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

Abstract: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modulated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.

Cited by 85 publications

References 39 publications

Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

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

Metalloproteinase-3 and -9 as Novel Markers in the Evaluation of Ulcerative Colitis Activity in Children

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