TY - JOUR T1 - Proinflammatory Cytokines Synergistically Enhance the Production of Chemokine Ligand 20 (CCL20) from Rheumatoid Fibroblast-like Synovial Cells <em>in vitro</em> and Serum CCL20 Is Reduced <em>in vivo</em> by Biologic Disease-modifying Antirheumatic Drugs JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.090132 SP - jrheum.090132 AU - Shin-Ya Kawashiri AU - Atsushi Kawakami AU - Naoki Iwamoto AU - Keita Fujikawa AU - Toshiyuki Aramaki AU - Mami Tamai AU - Kazuhiko Arima AU - Makoto Kamachi AU - Satoshi Yamasaki AU - Hideki Nakamura AU - Toshiyuki Tsurumoto AU - Masafumi Kono AU - Hiroyuki Shindo AU - Hiroaki Ida AU - Tomoki Origuchi AU - Katsumi Eguchi Y1 - 2009/10/01 UR - http://www.jrheum.org/content/early/2009/09/30/jrheum.090132.abstract N2 - Objective Chemokine ligand 20 (CCL20) is a selective ligand for chemokine receptor 6 (CCR6). We investigated, both in vitro and in vivo, whether CCL20 is critically involved in the disease process of rheumatoid arthritis (RA). Methods In vitro study investigated the effect of proinflammatory cytokines and biologic disease-modifying antirheumatic drugs (DMARD) on the production of CCL20 by rheumatoid fibroblast-like synovial cells (FLS). The in vivo role of CCL20 was studied by screening for serum CCL20 concentration in patients with RA during the therapeutic course of biologic DMARD, i.e., infliximab, etanercept, and tocilizumab. Results Spontaneous CCL20 production from rheumatoid FLS was minimal; however, its production was significantly stimulated by interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), or IL-17. IL-1ß was the most potent for stimulating the production of CCL20. CCL20 production was synergistically augmented by a combination of IL-1ß, TNF-α, and IL-17. In contrast, interferon-γ suppressed IL-1ß-induced CCL20 production. IL-6, in combination with soluble IL-6 receptor (sIL-6R), did not modulate CCL20 production, whereas IL-1ß-induced, TNF-α-induced, and IL-17-induced production were increased by IL-6. These production levels were clearly suppressed by biologic DMARD in vitro. Serum CCL20 was significantly higher in RA than in control subjects, and was clearly decreased by the treatment with infliximab, etanercept, and tocilizumab. Conclusion Proinflammatory cytokines modulate the production of CCL20 from FLS. Our data suggest that therapeutic efficacy of biologic DMARD may result from the inhibition of CCL20 production in rheumatoid synovium. ER -