Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation

INTRODUCTION: Spontaneous resorption of disc herniation (DH) after sciatica is well documented. The matrix metalloproteinases (MMP)-1 and MMP-3 are enzymes potentially involved in this process. Glucocorticoid injections are commonly used for treatment, and other anti-inflammatory molecules like tumo...

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Autores principales: Genevay, Stéphane, Finckh, Axel, Mezin, Françoise, Tessitore, Enrico, Guerne, Pierre-André
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003509/
https://www.ncbi.nlm.nih.gov/pubmed/19906289
http://dx.doi.org/10.1186/ar2858
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author Genevay, Stéphane
Finckh, Axel
Mezin, Françoise
Tessitore, Enrico
Guerne, Pierre-André
author_facet Genevay, Stéphane
Finckh, Axel
Mezin, Françoise
Tessitore, Enrico
Guerne, Pierre-André
author_sort Genevay, Stéphane
collection PubMed
description INTRODUCTION: Spontaneous resorption of disc herniation (DH) after sciatica is well documented. The matrix metalloproteinases (MMP)-1 and MMP-3 are enzymes potentially involved in this process. Glucocorticoid injections are commonly used for treatment, and other anti-inflammatory molecules like tumor necrosis factor (TNF) inhibitors are under clinical investigation. However, little is known about the effect of these molecules on DH resorption. METHODS: DH tissue was harvested from patients undergoing surgery for sciatica. Samples were thoroughly washed. Diced explants were cultured ex-vivo in 1) 0.5 ml Dulbecco's modified Eagle's medium (DMEM) 10% fetal calf serum (FCS), (controls), 2) recombinant interleukin 1 receptor antagonist (IL-1Ra), (100 ng/ml), 3) dexamethasone (10E-5 M), or 4) TNF inhibitor monoclonal antibody (10 μg/ml). Supernatants were harvested at 48 hours and frozen. Immunocapture activity assays determined total MMP activity, active MMP levels and pro-MMP levels. RESULTS: Fourteen DH tissue samples were analysed. Levels of all forms of MMP-3 were higher than the respective levels of MMP-1(P < 0.01). In particular, the median (interquartile range [IQR]) total MMP-3 level was 0.97 (0.47 - 2.19) ng/mg of tissue compared to 0.024 (0.01 - 0.07) ng/mg of total MMP-1 level (P < 0.01). Incubation with IL-1Ra, dexamethasone, or TNF inhibitors significantly decreased levels of all forms of MMP-3 (P < 0.05). Dexamethasone significantly decreased the ratio of active MMP-3 to total MMP-3 activity. A significant inhibitory effect of dexamethasone was observed only on active MMP-1, while IL-1 and TNF inhibitor had no significant effect on any form. CONCLUSIONS: MMP-3 appears to play a greater role than MMP-1 in DH resorption. Dexamethasone, IL-1-Ra and TNF inhibitor decreased active MMP-3, indicating that the clinical use of these drugs may affect the resorption of DH under certain conditions.
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spelling pubmed-30035092010-12-18 Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation Genevay, Stéphane Finckh, Axel Mezin, Françoise Tessitore, Enrico Guerne, Pierre-André Arthritis Res Ther Research Article INTRODUCTION: Spontaneous resorption of disc herniation (DH) after sciatica is well documented. The matrix metalloproteinases (MMP)-1 and MMP-3 are enzymes potentially involved in this process. Glucocorticoid injections are commonly used for treatment, and other anti-inflammatory molecules like tumor necrosis factor (TNF) inhibitors are under clinical investigation. However, little is known about the effect of these molecules on DH resorption. METHODS: DH tissue was harvested from patients undergoing surgery for sciatica. Samples were thoroughly washed. Diced explants were cultured ex-vivo in 1) 0.5 ml Dulbecco's modified Eagle's medium (DMEM) 10% fetal calf serum (FCS), (controls), 2) recombinant interleukin 1 receptor antagonist (IL-1Ra), (100 ng/ml), 3) dexamethasone (10E-5 M), or 4) TNF inhibitor monoclonal antibody (10 μg/ml). Supernatants were harvested at 48 hours and frozen. Immunocapture activity assays determined total MMP activity, active MMP levels and pro-MMP levels. RESULTS: Fourteen DH tissue samples were analysed. Levels of all forms of MMP-3 were higher than the respective levels of MMP-1(P < 0.01). In particular, the median (interquartile range [IQR]) total MMP-3 level was 0.97 (0.47 - 2.19) ng/mg of tissue compared to 0.024 (0.01 - 0.07) ng/mg of total MMP-1 level (P < 0.01). Incubation with IL-1Ra, dexamethasone, or TNF inhibitors significantly decreased levels of all forms of MMP-3 (P < 0.05). Dexamethasone significantly decreased the ratio of active MMP-3 to total MMP-3 activity. A significant inhibitory effect of dexamethasone was observed only on active MMP-1, while IL-1 and TNF inhibitor had no significant effect on any form. CONCLUSIONS: MMP-3 appears to play a greater role than MMP-1 in DH resorption. Dexamethasone, IL-1-Ra and TNF inhibitor decreased active MMP-3, indicating that the clinical use of these drugs may affect the resorption of DH under certain conditions. BioMed Central 2009 2009-11-11 /pmc/articles/PMC3003509/ /pubmed/19906289 http://dx.doi.org/10.1186/ar2858 Text en Copyright ©2009 Genevay et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Genevay, Stéphane
Finckh, Axel
Mezin, Françoise
Tessitore, Enrico
Guerne, Pierre-André
Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation
title Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation
title_full Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation
title_fullStr Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation
title_full_unstemmed Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation
title_short Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation
title_sort influence of cytokine inhibitors on concentration and activity of mmp-1 and mmp-3 in disc herniation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003509/
https://www.ncbi.nlm.nih.gov/pubmed/19906289
http://dx.doi.org/10.1186/ar2858
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