CCL18 Activates Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis
CCL18 Activates Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis
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DOI：
10.3899/jrheum.121412
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
A. Takayasu;Y. Miyabe;W. Yokoyama;K. Kaneko;S. Fukuda;N. Miyasaka;C. Miyabe;T. Kubota;T. Nanki
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文献类型：
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作者：
A. Takayasu;Y. Miyabe;W. Yokoyama;K. Kaneko;S. Fukuda;N. Miyasaka;C. Miyabe;T. Kubota;T. Nanki
致编辑：成纤维细胞样滑膜细胞（FLS）在类风湿性关节炎（RA）患者的滑膜组织中增殖，并由于产生多种细胞因子、趋化因子和基质金属蛋白酶（MMP）1而导致慢性炎症和关节软骨的破坏。CC趋化因子配体18（CCL 18）的表达在RA滑膜中显示增加2，3;然而，CCL 18的致病作用仍不清楚。在这项研究中，我们研究了最近确定的受体CCL 18，磷脂酰肌醇转移膜相关磷脂酰肌醇转移蛋白3（PITPNM 3）4在RA滑膜的表达，以及CCL 18对FLS的刺激作用。滑膜组织样品获自经历关节置换手术的RA（n = 4）和骨关节炎（OA）（n = 4）患者。RA患者的中位年龄为65岁（范围48-85岁），中位病程为9年（范围2.5-30年），中位C反应蛋白水平为1.23 mg/dl（范围0.68-2.85）。所有RA患者的类风湿因子和抗瓜氨酸蛋白抗体均呈阳性。所有受试者均提供知情同意书。实验方案事先得到了东京医科牙科大学伦理委员会的批准。在RA滑膜的滑膜衬里、下层衬里和血管周围区域中观察到CCL 18阳性细胞（图1A）。在OA滑膜中，CCL 18表达最小（图1C）。Western印迹分析显示，RA滑膜中的CCL 18表达显著高于OA滑膜中的CCL 18表达（图1 E、1F）。双重免疫荧光染色显示，大多数CD 68阳性巨噬细胞表达CCL 18（图1G-1 I），血管性血友病因子（vWF）阳性血管内皮细胞也表达CCL 18。Nanki，东京医科齿科大学医学和牙科科学研究生院医学和流变学系，1-5-45，Yushima，文京区，东京113-8519。电子邮件：nanki.rheu{at} tmd.ac.jp
To the Editor: Fibroblast-like synoviocytes (FLS) proliferate in the synovial tissue of patients with rheumatoid arthritis (RA), and contribute to chronic inflammation and the destruction of articular cartilage due to the production of a variety of cytokines, chemokines, and matrix metalloproteinases (MMP)1. The expression of CC chemokine ligand 18 (CCL18) was shown to be increased in the RA synovium2,3; however, the pathogenic role of CCL18 remains unclear. In this study, we investigated the expression of a recently identified receptor for CCL18, phosphatidylinositol transfer membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3)4 in the RA synovium, and the stimulatory effects of CCL18 on FLS. Synovial tissue samples were obtained from patients with RA (n = 4) and osteoarthritis (OA) (n = 4) undergoing joint replacement surgery. RA patients were a median 65 years old (range 48–85 yrs), with median disease duration 9 years (range 2.5–30 yrs) and median C-reactive protein level 1.23 mg/dl (range 0.68–2.85). All RA patients were positive for rheumatoid factor and anticitrullinated protein antibodies. All subjects provided informed consent. The experimental protocol was approved in advance by the Ethics Committee of Tokyo Medical and Dental University. CCL18-positive cells were observed in the synovial lining, sublining, and perivascular regions of the RA synovium (Figure 1A). CCL18 expression was minimal in the OA synovium (Figure 1C). Western blotting analysis showed that CCL18 expression was significantly higher in the RA synovium than in the OA synovium (Figure 1E, 1F). Double-immunofluorescence staining revealed that most CD68-positive macrophages expressed CCL18 (Figures 1G–1I), and von Willebrand factor (vWF)-positive vascular endothelial cells were also … Address correspondence to Dr. T. Nanki, Department of Medicine and Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. E-mail: nanki.rheu{at}tmd.ac.jp