Investigation of the role of IL-1 and TNF in matrix degradation in the intervertebral disc
Investigation of the role of IL-1 and TNF in matrix degradation in the intervertebral disc
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DOI：
10.1093/rheumatology/ken056
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发表时间：
2008-06-01
期刊：
影响因子：
5.5
通讯作者：
Freemont, A. J.
中科院分区：
文献类型：
--
作者：
Hoyland, J. A.;Le Maitre, C.;Freemont, A. J.
客观的。确定 IL-1 或 TNF 是否调节非退变或退变椎间盘 (IVD) 中的基质降解。方法。原位酶谱 (ISZ) 已用于研究 IL-1 和 TNF 在表征症状性 IVD 变性的基质降解中的作用。 ISZ 采用三种底物（明胶、胶原蛋白 II、酪蛋白）和四种不同的挑战：IL-1 β、IL-1 受体拮抗剂 (IL-1Ra)、TNF-α 和抗 TNF。结果。我们首次证明，虽然IL-1β会刺激完整人IVD组织中的基质降解，而IL-1受体拮抗剂会抑制完整人IVD组织中的基质降解，但TNF-α或抗TNF对这些基质的降解均没有任何可测量的影响。结论。这项研究解决了 IVD 生物学中当前存在争议的领域，即 IL-1 或 TNF 或两者是否参与驱动基质降解。我们的数据表明，IL-1 是 IVD 中介导基质降解的关键细胞因子，因此是治疗靶点。
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-1 beta, IL-1 receptor antagonist (IL-1Ra), TNF-alpha and anti-TNF.Results. We have shown for the first time that whilst IL-1 beta 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.