Iwamoto Takuji, Okamoto Hiroshi, Kobayashi Shu, Ikari Katsunori, Toyama Yoshiaki, Tomatsu Taisuke, Kamatani Naoyuki, Momohara Shigeki
Institute of Rheumatology, Tokyo Women's Medical University, Japan.
FEBS J. 2007 Sep;274(18):4904-12. doi: 10.1111/j.1742-4658.2007.06013.x.
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.
我们研究了单核细胞趋化因子（MCP）-4/CCL13在类风湿关节炎（RA）发病机制中的作用。MCP-4在RA患者的软骨中高表达。γ干扰素显著刺激人软骨细胞中MCP-4/CCL13的产生，并且与白细胞介素-1β或肿瘤坏死因子-α联合时这种效应增强。MCP-4/CCL13诱导成纤维样滑膜细胞中细胞外信号调节激酶的磷酸化并激活细胞增殖，而PD98059完全抑制这些效应。这些数据表明，γ干扰素与白细胞介素-1β/肿瘤坏死因子-α联合可激活RA关节软骨细胞产生MCP-4/CCL13，并且分泌的MCP-4/CCL13通过激活细胞外信号调节激酶丝裂原活化蛋白激酶级联反应增强成纤维样滑膜细胞增殖。
