CCL20 produced in the cytokine network of rheumatoid arthritis recruits CCR6+ mononuclear cells and enhances the production of IL-6

Abstract

Although a notable amount of CCL20 is detectable in the synovial fluid of human rheumatoid arthritis (RA), its role in the pathogenesis of RA remains to be determined. IL-1beta vigorously induced the production of CCL20 from FLSs of human RA and the production of CCL20 induced by TNF-alpha was partially attributed to a trace amount of IL-1beta induced by TNF-alpha. Although IL-6 failed to induce CCL20, TNF-alpha-induced IL-6 enhanced the production of CCL20 in an autocrine/paracrine manner. To determine the role of CCL20 and its sole receptor CCR6 in the recruitment of mononuclear cells (MNCs) into the inflamed joint of RA, conditioned medium of IL-1beta-stimulated FLSs was used in migration assays. The conditioned medium significantly recruited CCR6(+) MNCs in a CCL20-dependent manner. The production of CCL20 induced by TNF-alpha and IL-1beta was modified by helper-T-cell-derived cytokines. Interestingly, CCL20 enhanced the production of IL-6 coordinately with the stimulation of IL-17 but not with that of IFN-gamma. These findings imply FLSs stimulated by proinflammatory cytokines recruit CCR6(+) MNCs including IL-17-producing-helper T cells into the inflamed joint, leading to the enhancement of the production of CCL20, which chemokine and IL-17 coordinately induce proinflammatory cytokines.

Alpha-mangostin attenuates oxidative stress and inflammation in adjuvant-induced arthritic rats

“…Early phase elevated TNF-and IL-6 serum levels are the hallmark of RA [23]. In the present investigation, treatment with α-mangostin significantly downregulated TNF-α and IL-6 serum protein expression and upregulated paw tissue expression, which corroborates previous reports [24].…”

Comparison of Blood and Synovial Fluid Th17 and Novel Peptidase Inhibitor 16 Treg Cell Subsets in Juvenile Idiopathic Arthritis

“…Interestingly, we found low levels of MIPα (CCL3) but high levels of RANTES (CCL5) in the synovial fluid of our JIA patients, both ligands that bind CCR5. This result contrasts with data from RA patients in which high levels of both MIPα and RANTES have been reported [41][42][43][44] supporting the hypothesis that JIA and RA are clinically and mechanistically distinct arthritides.…”

Anti-inflammatory effect of Sanshuibaihu decoction may be associated with nuclear factor-κB and p38 MAPKα in collagen-induced arthritis in rat

“…As is known that cytokine network plays a key role in the inflammatory responses of RA (Williams et al, 2007;Tanida et al, 2009), while NF-B and MAPKs are essential for cytokine networktriggering and amplifying (Morel and Berenbaum, 2004). As a member of MAPKs family, p38 MAPK␣ is most widely expressed in RA synovial lining cells, vascular endothelial cells and osteoclast precursors (Korb et al, 2006;Mbalaviele et al, 2006).…”