Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA)
Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA)
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DOI：
10.1046/j.1365-2249.2000.01110.x
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发表时间：
2000-01-01
影响因子：
4.6
通讯作者：
Gabrielli, A
中科院分区：
文献类型：
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作者：
Luchetti, MM;Piccinini, G;Gabrielli, A
PTX3是一种分泌型分子，由一个类似于经典五肽(如C-反应蛋白)的C-末端结构域和一个无关的N-末端结构域组成。与经典的五肽不同，长五肽PTX3在不同类型的细胞中表达是对IL-1β和肿瘤坏死因子-α(TNF-α)的反应，而不是对IL-6的反应。本研究旨在探讨PTX3在类风湿关节炎中的表达。分离的RA和骨关节炎(OA)B型滑膜细胞在有无炎性细胞因子的情况下进行培养。Northern分析检测滑膜细胞PTX3mRNA的表达。用ELISA法测定滑膜细胞培养和滑液中PTX3的蛋白水平，用免疫组织化学方法检测PTX3在滑膜组织中的分布。肿瘤坏死因子-α可诱导骨性关节炎滑膜细胞高水平表达PTX3，而IL-1β、IL-6等细胞因子不能诱导其高水平表达PTX3。RA滑膜细胞不同于OA滑膜细胞，在没有刻意刺激的情况下，结构性地表达高水平的PTX3。抗肿瘤坏死因子-α抗体、IL-1受体拮抗剂或两者联合不能改变PTX3在RA滑膜细胞中的结构性表达。相反，干扰素-γ和转化生长因子-β抑制了PTX3在RA滑膜细胞中的结构性表达。RA患者关节液中PTX3免疫活性高于对照组，滑膜组织中含有PTX3免疫组织化学阳性的内皮细胞和滑膜细胞。综上所述，PTX3可能在类风湿关节炎炎症循环中发挥作用，其作为疾病活动性标志物的相关性值得进一步研究。
PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein (CRP)) and of an unrelated N-terminal domain. Unlike the classical pentraxins, the long pentraxin PTX3 is expressed in response to IL-1 beta and tumour necrosis factor-alpha (TNF-alpha), but not to IL-6, in various cell types. The present study was designed to investigate the expression of PTX3 in RA. Dissociated RA and osteoarthritis (OA) type B synoviocytes were cultured in the presence and in the absence of inflammatory cytokines. PTX3 mRNA expression in synoviocytes was evaluated by Northern analysis. PTX3 protein levels in synovial cell cultures and synovial fluid were estimated by ELISA, and PTX3 distribution in synovial tissues by immunohistochemical techniques. OA synoviocytes were induced to express high levels of PTX3 mRNA by TNF-alpha, but not by other cytokines including IL-1 beta and IL-6. RA synoviocytes, unlike OA synoviocytes, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in RA synoviocytes was not modified by anti-TNF-alpha antibodies, IL-1 receptor antagonist or a combination of the two agents. In contrast, interferon-gamma and transforming growth factor-beta inhibited PTX3 constitutive expression in RA synoviocytes. The joint fluid from RA patients contained higher levels of immunoreactive PTX3 than controls and the synovial tissue contained endothelial cells and synoviocytes positive for PTX3 by immunohistochemistry. In conclusion, PTX3 may play a role in inflammatory circuits of RA, and its relevance as a marker of disease activity deserves further study.