Effect of the anti-tumor necrosis factor-α antibody infliximab on the ex vivo mucosal matrix metalloproteinase–proteolytic phenotype in inflammatory bowel disease

Meijer, M.; Mieremet-Ooms, Marij A C; Duijn, Wim van; Zon, Annie M. Van der; Hanemaaijer, Roeland; Verheijen, J.H.; Hogezand, R. A. van; Lamers, C. B. H. W.; Verspaget, Hein W.

doi:10.1002/ibd.20051

Cited by 63 publications

(44 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This cytokine has pleiotropic effects in the bowel wall: it induces neoangiogenesis 40 ; activates macrophages to produce proinflammatory cytokines; favours Paneth cell death via necroptosis 41 ; augments apoptosis of intestinal epithelial cells 42 ; regu lates T cell apoptosis 40,43,44 ; and reduces production of tissue inhib itor of matrix metalloproteinases (MMPs) by fibroblasts to mediate tissue injury via activated MMPs 45 . Thus, anti TNF antibodies can suppress intestinal inflammation in IBD through several mechanisms.…”

Section: Classic Immunosuppressive Drugsmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

507

403

View full text Add to dashboard Cite

Inflammatory bowel diseases (including IBD, exempli fied by Crohn's disease and ulcerative colitis) are chronic relapsing disorders affecting the gastrointestinal tract. IBD has a progressive and destructive nature and, there fore, can cause various complications including steno ses, abscesses, fistulas, extraintestinal manifestations and colitis associated neoplasias and cancer 1,2 . Thus, effective therapeutic approaches are of high clinical rele vance in patients with IBD. This Review summarizes current therapeutic strategies and highlights emerging new treatment approaches for IBD with special refer ence to the proposed molecular mechanisms of action of anti inflammatory drugs. Current IBD therapiesClassic anti-inflammatory drugs. 5 Aminosalicylates (5 ASAs) are important anti inflammatory drugs that are frequently used for anti inflammatory therapy in patients with ulcerative colitis 3 . By contrast, 5 ASA based drugs show little or no efficacy in inducing res olution of clinical symptoms and tissue inflammation in patients with Crohn's disease 4 .5 ASAs are effective for induction and mainten ance of remission in ulcerative colitis and might also reduce the risk of developing colitis associated tumours in these patients 5 . Several mechanisms of action for 5 ASAs have been proposed, including reduction of prostaglandin synthesis via inhibition of cyclooxygenase, suppression of proinflammatory cytokine production and oxygen free radicals, inhib ition of lipoxygenase, blockade of neutrophil chemo taxis and mast cell activation, and impairment of nuclear factor κB activation (NF κB) in immune cells 3 . Moreover, studies in mice revealed that 5 ASA based drugs augment peroxisome proliferator activated receptor γ (PPARγ) expression and promote PPARγ translocation from the cytoplasm to the nucleus where they result in activation of peroxisome proliferator hormone response element driven genes to suppress colitis activity 6,7 .In addition to 5 ASAs, corticosteroids (systemically or topically delivered) have been used for remission induction in ulcerative colitis 2 . Although cortico steroids favour induction of remission in both ulcer ative colitis and Crohn's disease, they are not suitable for mainten ance of remission in IBD 1,2 . Mechanistically, gluco corticoids bind to a specific cytosolic receptor fol lowed by translocation of the complex to the nucleus to either activate or repress gene transcription (via bind ing to DNA corticosteroid response elements) 8,9 . Additionally, the glucocorticoid-receptor complex can inactivate pro inflammatory transcription factors such as NF κB and activator protein 1 (AP1) via proteinprotein inter actions, thereby preventing their activation of inflammatory mediators (for example, leukotrienes and cytokines such as IL 1 and IL 6). REVIEWS© 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

show abstract

Section: Classic Immunosuppressive Drugsmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

507

403

View full text Add to dashboard Cite

show abstract

“…Indeed, experimental data suggest that inhibition of MMP-9 may be of benefit in future strategies in IBD therapy [29,65]. It has also been suggested that infliximab therapy can induce a genotype-associated matrix protective phenotype by downregulating MMP-9 activity, which may contribute to the therapeutic efficacy of this drug in IBD [66]. It has also been proposed that anti-TNF therapy may enhance the inhibitor TIMP-1 production, which may reduce MMP activity and facilitate wound healing [67].…”

Section: Discussionmentioning

confidence: 99%

The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases

Lakatos

Hritz

Varga

et al. 2012

Dig Dis

View full text Add to dashboard Cite

Background: It has been suggested that matrix metalloproteinases (MMPs) may play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, the impact of serum MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] have scarcely been investigated in the same experimental setting in ulcerative colitis (UC) and Crohn’s disease (CD) as well as their correlation with IBD activity. Methods: MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 serum antigen levels were determined in 23 patients with UC, 25 patients with CD and 10 healthy control patients by enzyme-linked immunoassay technique. Statistical analysis with one-way ANOVA and Student’s t tests was performed. A linear regression analysis or a Spearman’s r test was used to assess correlation. Differences were considered significant with p < 0.05. Results: Serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly higher in UC and CD patients compared to controls. MMP-7 was also significantly higher in CD compared with controls. Elevated MMP-9 and TIMP-1 antigen levels showed significant positive correlation with disease activity of IBD. MMP-2 and TIMP-2 levels inversely correlated with CD activity. Significant correlations were found between MMP-9/TIMP-1 and MMP-2/TIMP-2 antigen levels in both UC and CD. Conclusions: We demonstrated that serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly increased in patients with UC and CD compared to controls. Our results suggest that MMPs and TIMPs may contribute to the inflammatory and remodeling processes in IBD. Serum MMP-9 and TIMP-1 might be useful as additional biomarkers in the assessment of IBD activity.

show abstract

“…Single-nucleotide polymorphism (SNP) analysis for MMP-2 À1306C4T and MMP-9 À1562C4T was performed by tetraprimer ARMS PCR, involving four oligonucleotide primers but no restriction enzymes, or RFLP-PCR, as described earlier (Meijer et al, 2006;Kubben et al, 2006a).…”

Section: Single-nucleotide Polymorphism Analysismentioning

confidence: 99%

MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not

et al. 2008

View full text Add to dashboard Cite

The prognostic significance of single-nucleotide polymorphisms (SNPs) and tumour protein levels of MMP-2 and MMP-9 was evaluated in 215 colorectal cancer patients. Single-nucleotide polymorphism MMP-2 À1306T and high MMP-2 levels were significantly associated with worse survival. Extreme tumour MMP-9 levels were associated with poor prognosis but SNP MMP-9 À1562C4T was not. Tumour MMP levels were not determined by their SNP genotypes.

show abstract

Effect of the anti-tumor necrosis factor-α antibody infliximab on the ex vivo mucosal matrix metalloproteinase–proteolytic phenotype in inflammatory bowel disease

Cited by 63 publications

References 50 publications

Current and emerging therapeutic targets for IBD

Current and emerging therapeutic targets for IBD

The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases

MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not

Contact Info

Product

Resources

About