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International Journal of Colorectal Disease

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01-10-2009 | Original Article

Changes in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinases (TIMP) expression profile in Crohn's disease after immunosuppressive treatment correlate with histological score and calprotectin values

Authors: Laura Mäkitalo, Taina Sipponen, Päivi Kärkkäinen, Kaija-Leena Kolho, Ulpu Saarialho-Kere

Published in: International Journal of Colorectal Disease | Issue 10/2009

Abstract

Background

Matrix metalloproteinases (MMPs) constitute a family of enzymes capable of degrading various extracellular matrices (ECM) and basement membrane components playing a role in ECM turnover. They activate and degrade signaling molecules, such as cytokines and chemokines. MMPs are involved in inflammation and have been implicated in tissue degradation and repair occurring in inflammatory bowel disease. The aim of this study was to investigate the MMP profile of intestinal Crohn's disease (CD) patients before and after immunosuppressive treatment (anti-TNF-α agents or corticosteroids and conventional immunosuppressants azathioprine or methotrexate) to learn more about the therapeutic pathways for immunosuppressive agents.

Methods

Expression of MMP-1, MMP-7, MMP-9, MMP-10, and MMP-26 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-3 was studied by immunohistochemistry in pretreatment and post-treatment tissue samples. Semiquantitative immunohistochemical scores were tested for correlations with fecal and serum inflammation markers as well as endoscopic and clinical disease activity scores.

Results

Neutrophil MMP-9 (p = 0.039) and MMP-26 (p = 0.030) and stromal TIMP-1 (p = 0.041) and TIMP-3 (p = 0.029) decreased along with treatment. However, expression of TIMP-3 by enterocytes tended to increase. Total histological score demonstrated positive correlation with neutrophil MMP-9 (p = 0.000), MMP-26 (p = 0.014), and macrophage TIMP-1 (p = 0.001). Calprotectin followed a similar pattern with stromal MMP-26 (p = 0.011), TIMP-1 (p = 0.000), and TIMP-3 (p = 0.001). Crohn's disease endoscopic index of severity (CDEIS) value correlated positively with macrophage TIMP-1 (p = 0.007) and stromal TIMP-3 (p = 0.005). Epithelial TIMP-3 presented with negative correlations with CDEIS (p = 0.006) and C-reactive protein values (p = 0.004).

Conclusions

Our results suggest that immunosuppressive drugs modulate disease activity in CD by downregulation of MMP-9 and MMP-26 positive neutrophils and stromal TIMP-1 and TIMP-3.

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Title: Changes in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinases (TIMP) expression profile in Crohn's disease after immunosuppressive treatment correlate with histological score and calprotectin values
Authors: Laura Mäkitalo
Taina Sipponen
Päivi Kärkkäinen
Kaija-Leena Kolho
Ulpu Saarialho-Kere
Publication date: 01-10-2009
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 10/2009
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-009-0756-5

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Springer Medicine

Changes in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinases (TIMP) expression profile in Crohn's disease after immunosuppressive treatment correlate with histological score and calprotectin values

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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