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-gamma significantly stimulated MCP-4/CCL13 production in human chondrocytes, and this effect was enhanced in combination with interleukin-1beta or tumor necrosis factor-alpha. 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-gamma in combination with interleukin-1beta/tumor necrosis factor-alpha 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.
Iwamoto
Takuji
T
Institute of Rheumatology, Tokyo Women's Medical University, Japan.
Okamoto
Hiroshi
H
Kobayashi
Shu
S
Ikari
Katsunori
K
Toyama
Yoshiaki
Y
Tomatsu
Taisuke
T
Kamatani
Naoyuki
N
Momohara
Shigeki
S
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism