Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile.
Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile.
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DOI：
10.1186/ar2275
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发表时间：
2007
影响因子：
4.9
通讯作者：
Freemont, Anthony J
中科院分区：
文献类型：
--
作者：
Le Maitre, Christine Lyn;Hoyland, Judith Alison;Freemont, Anthony J
下背痛是一种常见的使人衰弱的疾病。目前的证据表明椎间盘（IVD）退变和突出是主要原因，尽管其发病机制尚不清楚。虽然几种细胞因子与IVD变性和疝形成过程有关，但研究主要集中在白细胞介素1（IL-1）和肿瘤坏死因子α（TNFα）。然而，迄今为止，还没有研究同时在IVD变性或疝形成中研究这些细胞因子的表达，或者确定哪些可能是与这些疾病状态相关的主要细胞因子。应用定量真实的时间PCR和免疫组织化学方法，我们研究了IL-1β、TNFα及其受体在非变性、变性和疝出的人IVD中的基因和蛋白表达。IL-1β基因表达在IVD中的比例高于TNFα（79% vs 59%）。退行性和突出性IVD的两种细胞因子水平均高于非退行性IVD，尽管在退行性IVD中观察到IL-1β基因表达水平（1，300拷贝/100 ng cDNA）高于TNFα（250拷贝TNFα/100 ng cDNA）。与非退化性IVD相比，退化性IVD显示出高10倍的IL-1受体基因表达。此外，80%的退化性IVD细胞显示IL-1受体免疫阳性，而非退化性IVD细胞仅为30%。然而，与非退化性IVD相比，在退化性或突出性IVD中未观察到TNF受体I基因或蛋白表达增加。我们已经证明，尽管两种细胞因子都是由人IVD细胞产生的，但IL-1β在更多的IVD中以更高的水平表达，特别是在更退化的IVD中（4至12级）。重要的是，这项研究强调了在退化的IVD中IL-1受体I型而不是TNF受体I型的基因和蛋白质产生的增加。因此，数据表明，虽然两种细胞因子可能参与IVD变性的发病机制，但IL-1可能比TNFα具有更重要的作用，因此可能是治疗干预的更好靶点。
Low back pain is a common and debilitating disorder. Current evidence implicates intervertebral disc (IVD) degeneration and herniation as major causes, although the pathogenesis is poorly understood. While several cytokines have been implicated in the process of IVD degeneration and herniation, investigations have predominately focused on Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNFα). However, to date no studies have investigated the expression of these cytokines simultaneously in IVD degeneration or herniation, or determined which may be the predominant cytokine associated with these disease states. Using quantitative real time PCR and immunohistochemistry we investigated gene and protein expression for IL-1β, TNFα and their receptors in non-degenerate, degenerate and herniated human IVDs. IL-1β gene expression was observed in a greater proportion of IVDs than TNFα (79% versus 59%). Degenerate and herniated IVDs displayed higher levels of both cytokines than non-degenerate IVDs, although in degenerate IVDs higher levels of IL-1β gene expression (1,300 copies/100 ng cDNA) were observed compared to those of TNFα (250 copies of TNFα/100 ng cDNA). Degenerate IVDs showed ten-fold higher IL-1 receptor gene expression compared to non-degenerate IVDs. In addition, 80% of degenerate IVD cells displayed IL-1 receptor immunopositivity compared to only 30% of cells in non-degenerate IVDs. However, no increase in TNF receptor I gene or protein expression was observed in degenerate or herniated IVDs compared to non-degenerate IVDs. We have demonstrated that although both cytokines are produced by human IVD cells, IL-1β is expressed at higher levels and in more IVDs, particularly in more degenerate IVDs (grades 4 to 12). Importantly, this study has highlighted an increase in gene and protein production for the IL-1 receptor type I but not the TNF receptor type I in degenerate IVDs. The data thus suggest that although both cytokines may be involved in the pathogenesis of IVD degeneration, IL-1 may have a more significant role than TNFα, and thus may be a better target for therapeutic intervention.