Synoviocyte-Derived Angiopoietin-Like Protein 2 Contributes to Synovial Chronic Inflammation in Rheumatoid Arthritis
Synoviocyte-Derived Angiopoietin-Like Protein 2 Contributes to Synovial Chronic Inflammation in Rheumatoid Arthritis
复制标题
DOI：
10.2353/ajpath.2010.090865
复制
发表时间：
2010-05-01
影响因子：
6
通讯作者：
Oike, Yuichi
中科院分区：
文献类型：
--
作者：
Okada, Tatsuya;Tsukano, Hiroto;Oike, Yuichi
类风湿性关节炎（RA）是一种慢性炎症性疾病，以关节的对称性多关节滑膜炎为特征。源自RA关节内的浸润性炎性细胞和活化的驻留细胞的几种促炎细胞因子在引起炎症的过程中起着重要作用。然而，抗细胞因子治疗是有益的，但不是治愈性的，效果只是部分的，并且无反应是常见的。因此，已经做出努力来识别关节结构中的炎症的其他关键调节剂，以开发新的治疗方法来抑制RA中的滑膜炎症和关节破坏。脂肪组织来源的血管生成素样蛋白2（Angptl 2）激活内皮细胞中的炎性级联反应并诱导肥胖症中单核细胞/巨噬细胞的趋化性，导致脂肪组织内炎症的起始和传播以及肥胖症相关的代谢疾病。Angptl 2 mRNA和蛋白在RA患者增生的类风湿性滑膜中大量表达，尤其是在成纤维细胞样和巨噬细胞样滑膜细胞中，而在B和T淋巴细胞中不表达。与骨关节炎患者相比，RA患者关节中的Angptl 2浓度也显著增加，与RA相比，骨关节炎患者代表关节炎的显著较低炎症等级形式。值得注意的是，Angptl 2促进了RA患者滑液中CD 14（+）CD 16（-）单核细胞趋化活性的增加。因此，Angptl 2在RA发病机制中作为重要的类风湿性滑膜源性炎症介质发挥作用。(Am J Pathol 2010，176：2309-2319; DOI：10.2353/ajpath.2010.090865）
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetrical polyarticular synovitis of the diarthrodial joints. Several proinflammatory cytokines derived from both infiltrating inflammatory cells and activated resident cells within the RA joint play a fundamental role in the processes that cause inflammation. However, anticytokine treatment is beneficial but not curative, the effects are only partial, and nonresponses are common Therefore, an effort has been made to identify other key regulators of inflammation in articular structures to develop new therapies to suppress synovial inflammation and joint destruction in RA. Adipose tissue-derived angiopoietin-like protein 2 (Angptl2) activates an inflammatory cascade in endothelial cells and induces chemotaxis of monocytes/macrophages in obesity, resulting in initiation and propagation of inflammation within adipose tissues and obesity-related metabolic diseases. Angptl2 mRNA and protein are abundantly expressed in hyperplastic rheumatoid synovium of RA patients, especially in fibroblast-like and macrophage-like synoviocytes, but not in B and T lymphocytes. Angptl2 concentration in joints of RA patients was also significantly increased in comparison with patients with osteoarthritis, which in comparison with RA represents a significantly lower inflammatory grade form of arthritis. Notably, Angptl2 promoted increased chemotactic activities of CD14(+)CD16(-) monocytes from synovial fluid of RA patients. Therefore, Angptl2 acts as an important rheumatoid synovium-derived inflammatory mediator in RA pathogenesis. (Am J Pathol 2010, 176:2309-2319; DOI: 10.2353/ajpath.2010.090865)