Activation of interleukin-1 signaling cascades in normal and osteoarthritic articular cartilage
Activation of interleukin-1 signaling cascades in normal and osteoarthritic articular cartilage
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DOI：
10.2353/ajpath.2007.061083
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发表时间：
2007-09-01
影响因子：
6
通讯作者：
Aigner, Thomas
中科院分区：
文献类型：
--
作者：
Fan, Zhiyong;Soeder, Stephan;Aigner, Thomas
白细胞介素11-1是类风湿关节炎中最重要的分解代谢细胞因子之一。在这项研究中，我们感兴趣的是我们是否能确定IL-1在正常软骨和骨关节炎软骨中的表达和活性。IL-1β及其主要靶基因IL-6的mRNA在正常软骨中的表达水平很低，而在骨关节炎软骨中这些细胞因子的表达仅轻微上调，这表明IL-1信号在骨关节炎中不是主要事件。然而，参与IL-1信号通路的中枢介质[38-kd蛋白激酶、磷酸(P)-38-kd蛋白激酶、细胞外信号调节激酶1/2、P-细胞外信号调节激酶1/2、c-Jun NH2末端激酶1/2、P-c-Jun NH2末端激酶1/2和核因子kappaB]的免疫定位表明，这四个IL-1信号通路在正常和骨关节炎关节软骨细胞中起作用。在体内，我们发现IL-1的表达和信号机制在正常软骨的上部可检测到，而这些观察在骨关节炎软骨的上部更为明显。鉴于这些表达和分布模式，我们的数据支持IL-1在关节软骨病理生理学中的两个作用。首先，骨关节炎关节软骨上部的软骨细胞似乎激活了分解代谢信号通路，这可能是对外部IL-1从滑液中扩散的反应。其次，IL-1似乎参与了正常软骨组织的动态平衡，如基线表达模式和信号级联激活所显示的那样。
Interleukin (11)-1 is one of the most important catabolic cytokines in rheumatoid arthritis. in this study, we were interested in whether we could identify IL-1 expression and activity within normal and osteoarthritic cartilage. mRNA expression of IL-1 beta and of one of its major target genes, IL-6, was observed at very low levels in normal cartilage, whereas only a minor up-regulation of these cytokines was noted in osteoarthritic cartilage, suggesting that IL-1 signaling is not a major event in osteoarthritis. However, immunolocalization of central mediators involved in IL-1 signaling pathways [38-kd protein kinases, phospho (P)-38-kd protein kinases, extracellular signal-regulated kinase 1/2, P-extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase 1/2, P-c-Jun NH2-terminal kinase 1/2, and nuclear factor kappa B] showed that the four IL-1 signaling cascades are functional in normal and osteoarthritic articular chondrocytes. In vivo, we found that IL-1 expression and signaling mechanisms were detectible in the upper zones of normal cartilage, whereas these observations were more pronounced in the upper portions of osteoarthritic cartilage. Given these expression and distribution patterns, our data support two roles for IL-1 in the pathophysiology of articular cartilage. First, chondrocytes in the upper zone of osteoarthritic articular cartilage seem to activate catabolic signaling pathways that may be in response to diffusion of external IL-1 from the synovial fluid. Second, IL-1 seems to be involved in normal cartilage tissue homeostasis as shown by identification of baseline expression patterns and signaling cascade activation.