title: A role of monocyte chemoattractant protein-4 (MCP-4)/CCL13 from chondrocytes in rheumatoid arthritis.
abstract: 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.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Shu
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tomatsu
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
mesh_terms: 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