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

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Published in Arthritis Research and Therapy. 2009, vol. 11, no. 6, p. R169
Abstract 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 microg/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.
Keywords Anti-Inflammatory Agents/*pharmacologyAntibodies, Monoclonal/pharmacologyDexamethasone/pharmacologyFemaleHumansInterleukin 1 Receptor Antagonist Protein/pharmacologyIntervertebral Disc Displacement/complications/*enzymology/immunologyMaleMatrix Metalloproteinase 1/drug effects/*metabolismMatrix Metalloproteinase 3/drug effects/*metabolismMiddle AgedSciatica/etiology/immunologyTumor Necrosis Factor-alpha/antagonists & inhibitors
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PMID: 19906289
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Research group Mécanisme de l'inflammation articulaire (44)
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GENEVAY, Stéphane et al. Influence of cytokine inhibitors on concentration and activity of MMP-1 and MMP-3 in disc herniation. In: Arthritis Research and Therapy, 2009, vol. 11, n° 6, p. R169. https://archive-ouverte.unige.ch/unige:19530

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Deposited on : 2012-04-23

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