Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo
Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo
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DOI：
10.1006/cyto.2001.0939
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发表时间：
2001-10-07
期刊：
影响因子：
3.8
通讯作者：
Filvaroff, EH
中科院分区：
文献类型：
--
作者：
Cai, LP;Yin, JP;Filvaroff, EH
白细胞介素（IL-）17的过度表达最近已被证明与许多病理条件。由于IL-17在炎症性关节炎患者软骨周围的滑液中水平较高，因此本研究确定了IL-17对关节软骨的直接作用。如本文所示，IL-17是关节软骨外植体中基质分解的直接且有效的诱导剂和基质合成的抑制剂。这些作用部分由白血病抑制因子（LIF）介导，但不依赖于白细胞介素-1活性。IL-17诱导软骨组织中基质分解的机制似乎是由于刺激聚集蛋白聚糖酶的活性，而不是基质金属蛋白酶。然而，IL-17上调单层培养的软骨细胞中基质金属蛋白酶的表达。在体内，当IL-17注射到小鼠膝关节的关节内间隙中时，其诱导类似于炎性关节炎的表型。此外，发现相关蛋白IL-17 E对人关节软骨具有分解代谢活性。本研究描述了IL-17直接作用于软骨基质周转的机制。这些发现对于治疗退行性关节疾病如关节炎具有重要意义。(C)北京：科学出版社.
Overexpression of interleukin (IL-)17 has recently been shown to be associated with a number of pathological conditions. Because IL-17 is found at high levels in the synovial fluid surrounding cartilage in patients with inflammatory arthritis, the present study determined the direct effect of IL-17 on articular cartilage. As shown herein, IL-17 was a direct and potent inducer of matrix breakdown and an inhibitor of matrix synthesis in articular cartilage explants. These effects were mediated in part by leukemia inhibitory factor (LIF), but did not depend on interleukin-1 activity. The mechanism whereby IL-17 induced matrix breakdown in cartilage tissue appeared to be due to stimulation of activity of aggrecanase(s), not matrix metalloproteinase(s). However, IL-17 upregulated expression of matrix metalloproteinase(s) in chondrocytes cultured in monolayer. In vivo, IL-17 induced a phenotype similar to inflammatory arthritis when injected into the intra-articular space of mouse knee joints. Furthermore, a related protein, IL-17E, was found to have catabolic activity on human articular cartilage. This study characterizes the mechanism whereby IL-17 acts directly on cartilage matrix turnover. Such findings have important implications for the treatment of degenerative joint diseases such as arthritis. (C) 2001 Academic Press.