Galectin 3 and its binding protein in rheumatoid arthritis
Galectin 3 and its binding protein in rheumatoid arthritis
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DOI：
10.1002/art.11287
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发表时间：
2003-10-01
影响因子：
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通讯作者：
Neidhart, M
中科院分区：
文献类型：
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作者：
Ohshima, S;Kuchen, S;Neidhart, M
目标。以Galectin 1为对照，研究Galectin 3和Galectin 3结合蛋白(G3BP)在类风湿关节炎(RA)中的表达模式和作用，并探讨血清、滑液或细胞培养上清液中的可溶性Galectin 3和G3BP是否与RA相关。用原位杂交和免疫组织化学方法检测了RA和骨关节炎(OA)患者滑膜组织及健康对照组滑膜组织Galectin1、Galectin3和G3BP的表达。用双抗体夹心酶联免疫吸附试验(ELISA)检测RA、OA患者血清、滑液及细胞培养上清中Galectin 3、G3BP的水平。采用流式细胞术检测肿瘤坏死因子α(TNFpha)、白介素1β(IL-1β)和抗CD40单抗对RA和OA滑膜成纤维细胞内Galectin 3表达的影响。在RA滑膜中，Galectin 3信使RNA和蛋白表达于整个滑膜，而G3BP仅在骨质破坏部位表达。相反，Galectin 1在不同的RA标本中的表达并不一致，而且从未在侵袭部位发现。在骨性关节炎和正常滑膜组织中，仅有少量细胞表达Galectins和/或G3BP。Galectin 3在RA血清和滑液中升高，而G3BP仅在RA滑液中升高。在RA中，血清Galectin 3与C反应蛋白水平相关，而G3BP与关节破坏和/或滑膜细胞激活有关，这是通过软骨低聚基质蛋白水平来衡量的。体外培养的RA滑膜成纤维细胞培养上清液中半乳糖凝集素3的释放增加，而G3BP的分泌减少。在Galectin 3低基础表达的RA滑膜成纤维细胞中，TNFpha以剂量依赖的方式增加其细胞内Galectin 3的水平。而IL-1β和抗CD40单抗则无此作用。我们的数据表明Galectin 3和G3BP不仅参与炎症反应，而且有助于滑膜成纤维细胞的激活。肿瘤坏死因子α可促进半乳糖凝集素3在细胞内的积累。因此，Galectin 3和G3BP是RA疾病活动性的新标记物。
Objective. To characterize the expression pattern and role of galectin 3 and galectin 3 binding protein (G3BP) in rheumatoid arthritis (RA), in comparison with galectin 1, and to explore whether soluble galectin 3 and G3BP, investigated in serum, synovial fluid, or cell culture supernatant, are associated with disease.Methods. Synovial tissues from patients with RA or osteoarthritis (OA), as well as from healthy controls, were analyzed for galectins 1 and 3 and G3BP by in situ hybridization and immunohistochemistry. Levels of galectin 3 and G3BP in serum and synovial fluid from patients with RA and OA and controls, as well as in cell culture supernatants, were determined by enzyme-linked immunosorbent assay (ELISA). In vitro, the intracellular expression of galectin 3 in RA and OA synovial fibroblasts after modulation with tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and anti-CD40 monoclonal antibodies was measured by flow cytometry.Results. In RA, galectin 3 messenger RNA and protein stained throughout the synovial membrane, whereas G3BP was particularly expressed at sites of bone destruction. In contrast, the expression of galectin 1 was not uniform in different RA specimens, and was never found,at sites of invasion. In OA and normal synovial tissues, only a small number of cells were positive for galectins and/or G3BP. Galectin 3 was elevated in RA sera and synovial fluids, whereas G3BP was increased in RA synovial fluids only. In RA, serum galectin 3 correlated with C-reactive protein levels, whereas G3BP was associated with joint destruction and/or synovial cell activation as measured by the levels of cartilage oligomeric matrix protein. In vitro, RA synovial fibroblasts showed an increased release of galectin 3 into culture medium, as measured by ELISA, but decreased secretion of G3BP. In RA synovial fibroblasts with low basal expression of galectin 3, TNFalpha increased its intracellular level in a dose-dependent manner. In contrast, IL-1beta or anti-CD40 monoclonal antibodies showed no effect.Conclusion. Our data indicate that galectin 3 and G3BP are not only involved in inflammation, but also contribute to the activation of synovial fibroblasts. The intracellular accumulation of galectin 3 can be enhanced by TNFalpha. Thus, galectin 3 and G3BP represent novel markers of disease activity in RA.