Production of the chemokine eotaxin-1 in osteoarthritis and its role in cartilage degradation.
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.
Hsu
Yi-Hsin
YH
Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC.
Hsieh
Ming-Shium
MS
Liang
Yu-Chih
YC
Li
Chao-Yi
CY
Sheu
Ming-Thau
MT
Chou
Der-Tsay
DT
Chen
Tzeng-Fu
TF
Chen
Chien-Ho
CH
D002358:Cartilage, Articular / Q000473:pathology*; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D019742:Chemokines, CC / Q000378:metabolism*; D002631:Chemotactic Factors, Eosinophil / Q000378:metabolism*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C515456:CCL11 protein, human; C111835:CCL2 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D007375:Interleukin-1; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3