IL-17RA and IL-17RC Receptors Are Essential for IL-17A-Induced ELR super(+) CXC Chemokine Expression in Synoviocytes and Are Overexpressed in Rheumatoid Blood

IL-17A is a cytokine secreted by the newly described Th17 cells implicated in rheumatoid arthritis (RA). Less is known about its receptors in synoviocytes. IL-17RA and IL-17RC were found to be overexpressed in RA peripheral whole blood and their expression was detected locally in RA synovium. In vit...

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Published in:The Journal of immunology (1950) 2008-01, Vol.180 (1), p.655-663
Main Authors: Zrioual, Saloua, Toh, Myew-Ling, Tournadre, Anne, Zhou, Yuan, Cazalis, Marie-Angelique, Pachot, Alexandre, Miossec, Vincent, Miossec, Pierre
Format: Article
Language:English
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Summary:IL-17A is a cytokine secreted by the newly described Th17 cells implicated in rheumatoid arthritis (RA). Less is known about its receptors in synoviocytes. IL-17RA and IL-17RC were found to be overexpressed in RA peripheral whole blood and their expression was detected locally in RA synovium. In vitro, IL-17A synergized with TNF- alpha to induce IL-6, IL-8, CCL-20, and matrix metalloproteinase-3. Using microarrays, a specific up-regulation of Glu-Leu-Arg super(+) CXC chemokines was observed in IL-17A-treated synoviocytes. Using both posttranslational inhibitions by silencing interfering RNA and extracellular blockade by specific inhibitors, we showed that both IL-17RA and IL-17RC are implicated in IL-17A-induced IL-6 secretion, whereas in the presence of TNF- alpha , the inhibition of both receptors was needed to down-regulate IL-17A-induced IL-6 and CCL-20 secretion. Thus, IL-17A-induced IL-6, IL-8, and CCL20 secretion was dependent on both IL-17RA and IL-17RC, which are overexpressed in RA patients. IL-17A-induced pathogenic effects may be modulated by IL-17RA and/or IL-17RC antagonism.
ISSN:0022-1767