title: Regulation of MMP-3 expression and secretion by the chemokine eotaxin-1 in human chondrocytes.
abstract: BACKGROUND
  Osteoarthritis (OA) is characterized by the degradation of articular cartilage, marked by the breakdown of matrix proteins. Studies demonstrated the involvement of chemokines in this process, and some may potentially serve as diagnostic markers and therapeutic targets; however, the underlying signal transductions are not well understood.
  
  
  METHODS
  We investigated the effects of the CC chemokine eotaxin-1 (CCL11) on the matrix metalloproteinase (MMP) expression and secretion in the human chondrocyte cell line SW1353 and primary chondrocytes.
  
  
  RESULTS
  Eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Inhibitors of extracellular signal-regulated kinase (ERK) and p38 kinase were able to repress eotaxin-1-induced MMP-3 expression. On the contrary, Rp-adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP receptors, and H-89, a protein kinase A (PKA) inhibitor, markedly enhanced eotaxin-1-induced MMP-3 expression. These results suggest that MMP-3 expression is specifically mediated by the G protein-coupled eotaxin-1 receptor activities. Interestingly, little amount of MMP-3 protein was detected in the cell lysates of eotaxin-1-treated SW1353 cells, and most of MMP-3 protein was in the culture media. Furthermore we found that the eotaxin-1-dependent MMP-3 protein secretion was regulated by phospholipase C (PLC)-protein kinase C (PKC) cascade and c-Jun N-terminal kinase (JNK)/mitogen-activated protein (MAP) kinase pathways. These data indicate a specific regulation of MMP-3 secretion also by eotaxin-1 receptor activities.
  
  
  CONCLUSIONS
  Eotaxin-1 not only induces MMP-3 gene expression but also promotes MMP-3 protein secretion through G protein-coupled eotaxin-1 receptor activities. Chemokines, such as eotaxin-1, could be a potential candidate in the diagnosis and treatment of arthritis.
authors: School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.
authors: Pin-Zhir
authors: PZ
authors: Chao
authors: Ming-Shium
authors: MS
authors: Hsieh
authors: Chao-Wen
authors: CW
authors: Cheng
authors: Yung-Feng
authors: YF
authors: Lin
authors: Chien-Ho
authors: CH
authors: Chen
mesh_terms: D045744:Cell Line, Tumor; D054413:Chemokine CCL11 / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D019902:Chondrocytes / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C515456:CCL11 protein, human; C111835:CCL2 protein, human; C483024:CCL5 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D012333:RNA, Messenger; D019278:Matrix Metalloproteinase 3