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. 2017;2(3):27.
doi: 10.3390/jfmk2030027. Epub 2017 Aug 2.

A Role for Soluble IL-6 Receptor in Osteoarthritis

Graham Akeson  1 , Charles J Malemud  1   2
Affiliations

A Role for Soluble IL-6 Receptor in Osteoarthritis

Graham Akeson et al. J Funct Morphol Kinesiol. 2017.

Abstract

Interleukin-6 (IL-6) is one of several pro-inflammatory cytokines present at elevated levels in the synovial fluid of individuals with confirmed clinical diagnosis of rheumatoid arthritis (RA) and osteoarthritis (OA). The mechanism of action of IL-6 was shown to involve its capacity to interact with a membrane-bound IL-6 receptor (mIL-6Rα), also known as the "classical" IL-6 pathway, or through its interaction with a soluble IL-6 receptor (sIL-6R) termed the "trans-signaling" pathway. Activation of downstream signaling is transduced via these IL-6 receptors and principally involves the Janus Kinase/Signal Transduction and Activators of Transcription (JAK/STAT) signaling pathway that is further regulated by glycoprotein-130 (gp130) interacting with the IL-6/mIL-6R complex. Phosphorylation of STAT proteins via JAK activation facilitates STAT proteins to act as transcription factors in inflammation. However, the biological function(s) of the sIL-6R in human chondrocytes requires further elucidation, although we previously showed that exogenous sIL-6R significantly suppressed the synthesis of neutrophil gelatinase-associated lipocalin (NGAL) in the immortalized line of human chondrocytes, C28/I2. NGAL was shown to regulate the activity of matrix metalloproteinase-9 (MMP-9), whose activity is crucial in OA for the destruction of articular cartilage. The "shedding" of sIL-6R from the plasma membrane is carried out by a family of enzymes known as A Distintegrin and Metalloproteinase (ADAM), which are also elevated in OA. In this paper, we have systematically reviewed the role played by IL-6 in OA. We have proposed that sIL-6R may be an important target for future drug development in OA by ameliorating cartilage extracellular protein degradation.

Keywords: a disintegrin and metalloproteinase; cytokines; inflammation; interleukin-6; interleukin-6 receptor; osteoarthritis; signal transduction.

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Conflict of interest statement

Conflicts of Interest: The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The general structure of snake venom metalloproteinases (SVMPs), A Distintegrin and Metalloproteinase (ADAMs), and ADAMTSs.
See this image and copyright information in PMC

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