Elsevier

Cytokine

Volume 16, Issue 1, October 2001, Pages 10-21
Cytokine

Regular Articles
PATHWAYS BY WHICH INTERLEUKIN 17 INDUCES ARTICULAR CARTILAGE BREAKDOWN IN VITRO AND IN VIVO

https://doi.org/10.1006/cyto.2001.0939Get rights and content

Abstract

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.

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    • Interleukin-17 in veterinary animal species and its role in various diseases: A review

      2013, Cytokine
      Citation Excerpt :

      In the same study, IL-17 was shown to induce the expression of MMP-1, MMP-3 and MMP-13 in bovine chondrocytes [99]. Furthermore, IL-17 was able to stimulate aggrecanase activity in bovine and porcine cartilage during the breakdown [100]. The induction of MMP-3, MMP-13 and aggrecanase-1 expression is dependent on the phosphorylation of mitogen-activated protein kinases: ERK, p38 and JNK proteins; AP-1 and NF-κB transcription factors [101].

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    Correspondence to: Dr Ellen H. Filvaroff, Department of Molecular Oncology, Genentech Inc., MS 37, 1 DNA Way, South San Francisco, CA 94080-4990, USA. Tel: 650-225-1159; Fax: 650-225-6497; E-mail:[email protected]

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