Eotaxin-1/CCL11 is involved in cell migration in rheumatoid arthritis

Abstract

Eotaxin-1 (CCL11) induces the migration of different leukocyte types by interacting with CCR3. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are pathogenic effectors and a major CCR3-expressing cell. The aim of this study was to investigate the expression and function of CCL11 in RA FLS. The expression of CCL11 and CCR3 was evaluated by ELISA, immunofluorescence and quantitative PCR analysis. The CCL11 levels in serum and synovial fluids (SFs) from RA patients were significantly higher than those in serum from healthy controls and SFs from osteoarthritis patients. CCL11 and CCR3 were expressed in the RA synovial tissue lining layers. The secretion of CCL11 in RA FLS-conditioned medium and the mRNA expression of CCL11 and CCR3 were induced by TNF-α. Furthermore, CCL11 induced the mRNA expression of CCL11 and CCR3. Application of a CCR3 antagonist reduced TNF-α-induced CCL11 secretion from RA FLS. CCL11 induced the migration of RA FLS and monocytes. RA FLS migration was decreased by treatment with CCL11 siRNA. The migration of monocytes to medium conditioned with CCL11 siRNA-transfected and TNF-α-stimulated RA FLS was reduced. These data indicate that the self-amplification of CCL11 via CCR3 may play an important role in cell migration in RA.

Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis

“…CCL11 and CCR3 production was proven in synovial tissue and synoviocytes of RA-affected joints, with the expression being stimulated by TNF and CCL11 itself. It was also confirmed that chemokine promotes synoviocytes migration during RA [ 18 ]. CCL11/CCR3 axis is also believed to affect bone destruction [ 19 ].…”

“…C–C motif ligand 11 chemokine (CCL11), also described as eotaxin, is a ligand for C–C chemokine receptor 3 (CCR3) with the capacity to bind to other receptors as well [ 18 ]. CCL11 is secreted by: endothelial and epithelial cells, eosinophils, fibroblasts, keratinocytes, smooth muscle cells or chondrocytes [ 19 ], and its expression is induced by TNF and IL-4 [ 20 ].…”

“…CCL11 is secreted by: endothelial and epithelial cells, eosinophils, fibroblasts, keratinocytes, smooth muscle cells or chondrocytes [ 19 ], and its expression is induced by TNF and IL-4 [ 20 ]. It affects migration and activation of various leukocytes including: mast cells, eosinophils, Th2 lymphocytes, basophils, neutrophils and macrophages [ 18 , 19 , 21 ]. CCL11 and CCR3 production was proven in synovial tissue and synoviocytes of RA-affected joints, with the expression being stimulated by TNF and CCL11 itself.…”

“…Similar results have been published by Wakabayashi et al when comparing protein serum levels between newly diagnosed RA sufferers and healthy controls as well as synovial fluid concentrations between RA group and OA subjects. Authors also revealed correlation between synovial fluid quantities of CCL11 and TNF and concluded chemokines' responsibility for destructive activity of synoviocytes [ 18 ]. Increased plasma CCL11 concentration in newly diagnosed RA patients was also described by Kokkonen et al Group even indicated it as one of the most important factors that shows altered expression due to RA onset [ 15 ].…”

Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling

“…Eotaxin is a CC chemokine ligand (CCL) with diverse immunoreactivity, and composes of eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26) (37)(38)(39)(40). Previous studies reported that eotaxin was a pivotal mediator for promoting migration, activation and maturity of eosinophils, and high levels of eotaxin facilitated local and systemic eosinophils recruitment which were involved in the pathophysiology of various autoimmune and inflammatory diseases (41)(42)(43). A recent publication demonstrated that plasma eotaxin concentrations were elevated in chronic rhinosinusitis patients and eotaxin-3 levels positively associated with the degree of mucosal eosinophil infiltration, which FGF, fibroblast growth factor; NGF, nerve growth factor; CTACK, cutaneous T cell attracting chemokine; G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte-macrophage colony stimulating factor; GRO, growth-regulated oncogene; HGF, hepatocyte growth factor; IFN, interferon; IL, interleukin; IP, interferon-inducible protein; LIF, leukemia inhibitory factor; MCP, monocyte chemotactic protein; M-CSF, macrophage colony stimulating factor; MIF, macrophage migration inhibitory factor; MIG, monokine induced by interferon-gamma; MIP, macrophage inflammatory protein; PDGF, platelet-derived growth factor; RANTES, regulated on activation in normal T-cell expressed and secreted; SCF, stem cell factor; SCGF, stem cell growth factor; SDF, stromal cell-derived factor; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor related apoptosis inducing ligand; VEGF, vascular endothelial cell growth factor.…”