J A Hoyland1, C Le Maitre, A J Freemont. 1. Tissue Injury and Repair Group, Research School in Clinical and Laboratory Sciences, Stopford Building, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Abstract
OBJECTIVE: To establish if IL-1 or TNF regulates matrix degradation in the non-degenerate or degenerate intervertebral disc (IVD). METHODS: In situ zymography (ISZ) has been used to investigate the role of IL-1 and TNF in the matrix degradation characterizing symptomatic IVD degeneration. ISZ employed three substrates (gelatin, collagen II, casein) and four different challenges, IL-1beta, IL-1 receptor antagonist (IL-1Ra), TNF-alpha and anti-TNF. RESULTS: We have shown for the first time that whilst IL-1beta will stimulate and IL-1 receptor antagonist will inhibit matrix degradation in intact human IVD tissue, neither TNF-alpha nor anti-TNF have any measurable effect on degradation of these matrices. CONCLUSION: This study has addressed a current area of controversy in IVD biology, namely, whether either IL-1 or TNF or both are involved in driving matrix degradation. Our data indicate that IL-1 is a key cytokine mediating matrix degradation in the IVD and therefore a therapeutic target.
OBJECTIVE: To establish if IL-1 or TNF regulates matrix degradation in the non-degenerate or degenerate intervertebral disc (IVD). METHODS: In situ zymography (ISZ) has been used to investigate the role of IL-1 and TNF in the matrix degradation characterizing symptomatic IVD degeneration. ISZ employed three substrates (gelatin, collagen II, casein) and four different challenges, IL-1beta, IL-1 receptor antagonist (IL-1Ra), TNF-alpha and anti-TNF. RESULTS: We have shown for the first time that whilst IL-1beta will stimulate and IL-1 receptor antagonist will inhibit matrix degradation in intact humanIVD tissue, neither TNF-alpha nor anti-TNF have any measurable effect on degradation of these matrices. CONCLUSION: This study has addressed a current area of controversy in IVD biology, namely, whether either IL-1 or TNF or both are involved in driving matrix degradation. Our data indicate that IL-1 is a key cytokine mediating matrix degradation in the IVD and therefore a therapeutic target.
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