{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:55:20Z","timestamp":1772819720762,"version":"3.50.1"},"reference-count":33,"publisher":"The Journal of Rheumatology","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>To compare levels of the chemokine CCL20 and its receptor CCR6 in donor, osteoarthritic (OA), and rheumatoid arthritis (RA) synovium; and to determine the molecular mechanism of cellular activation induced by chemokine\/receptor ligation in human fibroblast-like synoviocytes (FLS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Synovia and isolated FLS from donor, OA, and RA joints were analyzed for CCL20 and CCR6 expression by RT-PCR and immunohistochemistry. The effect of CCL20 on cytokines and mediators of cartilage degradation was examined by PCR for mRNA expression levels and ELISA, and Western blotting for protein. CCL20-dependent transcriptional and posttranscriptional activation of target genes was monitored using reporter constructs and luciferase assays in transfected donor FLS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>CCL20 and CCR6 proteins were abundantly expressed in RA synovial lining cells compared to donor or OA synovia as judged by immunohistochemistry. RT-PCR of synovial extracts confirmed the predominance of CCL20\/CCR6 mRNA expression in RA synovium. CCL20 mRNA expression was low in donor FLS, but increased dramatically after stimulation with recombinant human (rh) interleukin 1\u00df (IL-1\u00df). rhCCL20 increased mRNA and protein expression of COX-2, IL-1\u00df, tumor necrosis factor-\u03b1, IL-6, and the matrix-destructive metalloprotease MMP-3 in donor FLS cultures. High constitutive levels of IL-6 were released from RA synovia; CCL20-induced expression of IL-6 occurred through an NSAID\/COXIB-sensitive process. CCL20-induced expression of COX-2 was mediated by a PLCP1\/PKC\u03b1\/MEK1\/2\/ERK1\/2-dependent pathway involving both transcriptional and posttranscriptional mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>CCL20\/CCR6 may play an important role in the pathogenesis of RA by assembling the molecular and cellular components orchestrating synovitis.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.110049","type":"journal-article","created":{"date-parts":[[2011,7,4]],"date-time":"2011-07-04T12:20:12Z","timestamp":1309782012000},"page":"1858-1865","source":"Crossref","is-referenced-by-count":23,"title":["CCL20 Stimulates Proinflammatory Mediator Synthesis in Human Fibroblast-like Synoviocytes Through a MAP Kinase-dependent Process with Transcriptional and Posttranscriptional Control"],"prefix":"10.3899","volume":"38","author":[{"given":"NADA","family":"ALAAEDDINE","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"GEORGE","family":"HILAL","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RAFFIC","family":"BADDOURA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JOHN","family":"ANTONIOU","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JOHN A.","family":"Di BATTISTA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2262","published-online":{"date-parts":[[2011,7,1]]},"reference":[{"key":"2018112909265783000_38.9.1858.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2007.04.005"},{"key":"2018112909265783000_38.9.1858.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60008-8"},{"key":"2018112909265783000_38.9.1858.3","doi-asserted-by":"crossref","unstructured":"Tak PP . 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Prostaglandin E2: a central mediator of cytokine cell signaling through post-transcriptional and translational regulatory mechanisms in human synovial fibroblasts (HSF) [thesis]. Montreal: Department of Anatomy and Cell Biology, McGill University; 2005."},{"key":"2018112909265783000_38.9.1858.32","unstructured":"Gerarduzzi C . Characterizing the activating and attenuating signal scaffolding units of the PGE2-EP receptor system in normal and arthritic human synovial fibroblasts [thesis]. 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