tailieunhanh - Báo cáo khoa học: A role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 from chondrocytes in rheumatoid arthritis

We studied the role of monocyte chemoattractant (MCP)-4⁄CCL13 in the pathogenesis of rheumatoid arthritis (RA). MCP-4 was highly expressed in cartilage from RA patients. Interferon-c significantly stimulated MCP-4⁄ CCL13 production in human chondrocytes, and this effect was enhanced in combination with interleukin-1b or tumor necrosis factor-a. | ễFEBS Journal A role of monocyte chemoattractant protein-4 MCP-4 CCL13 from chondrocytes in rheumatoid arthritis Takuji Iwamoto1 2 Hiroshi Okamoto1 Shu Kobayashi1 2 Katsunori Ikari1 Yoshiaki Toyama2 Taisuke Tomatsu1 Naoyuki Kamatani1 and Shigeki Momohara1 1 Institute of Rheumatology Tokyo Women s MedicalUniversity Japan 2 Department of Orthopedic Surgery Schoolof Medicine Keio University Tokyo Japan Keywords chondrocytes extracellular signal-regulated kinase ERK monocyte chemoattractant protein-4 MCP-4 CCL13 rheumatoid arthritis Correspondence H. Okamoto Institute of Rheumatology Tokyo Women s MedicalUniversity 10-22 Kawada-cho Shinjuku Tokyo 162-0054 Japan Fax 81 3 5269 1726 Tel 81 3 5269 1725 E-mail hokamoto@ Received 14 April 2007 revised 6 July 2007 accepted 26 July 2007 We studied the role of monocyte chemoattractant MCP -4 CCL13 in the pathogenesis of rheumatoid arthritis RA . MCP-4 was highly expressed in cartilage from RA patients. Interferon-y significantly stimulated MCP-4 CCL13 production in human chondrocytes and this effect was enhanced in combination with interleukin-1 b or tumor necrosis factor-a. MCP-4 CCL13 induces the phosphorylation of extracellular signal-regulated kinase in fibroblast-like synoviocytes and activates cell proliferation and PD98059 completely inhibits these effects. These data suggest that interferon-y in combination with interleukin-1 b tumor necrosis factor-a activates the production of MCP-4 CCL13 from chondrocytes in RA joints and that secreted MCP-4 CCL13 enhances fibroblast-like synoviocyte proliferation by activating the extracellular signal-regulated kinase mitogen-activated protein kinase cascade. doi Rheumatoid arthritis RA is a chronic symmetric polyarticular joint disease that primarily affects the small joints of the hands and feet 1 . It is characterized by infiltration of inflammatory cells such as monocytes and T-lymphocytes into the joints leading to synovial .