Production of the chemokine eotaxin‐1 in osteoarthritis and its role in cartilage degradation

Abstract

The expression of the chemokine, eotaxin-1, and its receptors in normal and osteoarthritic human chondrocytes was examined, and its role in cartilage degradation was elucidated in this study. Results indicated that plasma concentrations of eotaxin-1 as well as the chemokines, RANTES, and MCP-1alpha, were higher in patients with osteoarthritis (OA) than those in normal humans. Stimulation of chondrocytes with IL-1beta or TNF-alpha significantly induced eotaxin-1 expression. The production of eotaxin-1 induced expression of its own receptor of CCR3 and CCR5 on the cell surface of chondrosarcomas, suggesting that an autocrine/paracrine pathway is involved in eotaxin-1's action. In addition, eotaxin-1 markedly increased the expressions of MMP-3 and MMP-13 mRNA, but had no effect on TIMP-1 expression in chondrocytes. However, pretreatment of anti-eotaxin-1 antibody significantly decreased the MMP-3 expression induced by IL-1beta. These results first demonstrate that human chondrocytes express the chemokine, eotaxin-1, and that its expression is induced by treatment with IL-1beta and TNF-alpha. The cytokine-triggered induction of eotaxin-1 further results in enhanced expressions of its own receptor of CCR3, CCR5, and MMPs, suggesting that eotaxin-1 plays an important role in cartilage degradation in OA.

Disease‐modifying effects of Glucosamine HCl involving regulation of metalloproteinases and chemokines activated by interleukin‐1β in human primary synovial fibroblasts

“…The production of chemokines further stimulated expressions of their own receptors and destroyed enzymes of MMPs, which are associated with joint inflammation and cartilage degradation [Hsu et al, 2004]. Ma et al [2002] reported that GLN is an efficacious agent for suppressing activation of T-cells and dendritic cells, two crucial cells involved in immune responses.…”

Melatonin promoted chemotaxins expression in lung epithelial cell stimulated with TNF-α

“…As IL-1β and TNF-α have similar effect on the expression of many chemotaxins[14,15], we chose TNF-α as the representative pro-inflammatory cytokines in the asthmatic lung in this study. After the cells became confluent, the medium was changed to serum-free DMEM medium for 12 h. A549 cells were then exposed to increasing concentrations of melatonin (10 -10 , 10 -9 , 10 -8 , 10 -7 , 10 -6 M, the physiology concentration are 10 -9 to 10 -7 M during day and night[16]) (Sigma, St. Louis, MO, USA) and TNF-α (100 ng/ml) (Sigma), for 12 h. The cells were also stimulated with a combination of melatonin (10 -10 , 10 -9 , 10 -8 , 10 -7 , 10 -6 M) and TNF-α (100 ng/ml).…”

Immunopathogenesis of osteoarthritis

“…Expression of IL-8/CXCL-8/Kc was, recently, shown to be stimulated by mechanical, inflammatory and metabolic stresses [106]. Hsu et al reported higher levels of eotaxin-1/CCL-11 in OA patients compared to controls and there was an increase in expression of eotaxin-1/CCL-11 upon treatment of chondrocytes with IL-1β and TNF-α [107]. Further, treatment of chondrocytes with eotaxin-1/CCL-11 resulted in increased expression of its receptors CCR-3 and CCR-5 and cartilage degradation enzymes MMP-3 and MMP-13 [107].…”

“…Hsu et al reported higher levels of eotaxin-1/CCL-11 in OA patients compared to controls and there was an increase in expression of eotaxin-1/CCL-11 upon treatment of chondrocytes with IL-1β and TNF-α [107]. Further, treatment of chondrocytes with eotaxin-1/CCL-11 resulted in increased expression of its receptors CCR-3 and CCR-5 and cartilage degradation enzymes MMP-3 and MMP-13 [107]. Brul et al detected the expression of CCR-5 on synovial fibroblasts from OA and RA patients.…”