Excitatory amino acid transporters expressed by synovial fibroblasts in rats with collagen-induced arthritis
Excitatory amino acid transporters expressed by synovial fibroblasts in rats with collagen-induced arthritis
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DOI：
10.1016/j.bcp.2005.09.010
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发表时间：
2005-12-05
影响因子：
5.8
通讯作者：
Yoneda, Y
中科院分区：
文献类型：
--
作者：
Hinoi, E;Ohashi, R;Yoneda, Y
虽然先前的研究已经证明关节炎患者滑液中脑神经递质谷氨酸（Glu）水平升高，但迄今为止，对Glu在关节滑膜组织中的可能作用并没有太多关注。在从雄性刘易斯大鼠膝关节制备的培养滑膜成纤维细胞中，首次显示了谷氨酸天冬氨酸转运蛋白、谷氨酸转运蛋白-1和兴奋性氨基酸载体-1（EAAC 1）以及特定的亲离子型和亲代谢型Gln受体的mRNA组成型表达。免疫组化分析显示，高定位的免疫反应EAAC 1在滑膜组织。在培养的滑膜成纤维细胞中，[H-3]Glu的蓄积以温度和钠依赖性方式发生，Km分别为23.1 +/- 1.1 μ M和V-max分别为237.1 +/- 31.1 pmol（mg蛋白/min）。在免疫II型胶原诱导的关节炎大鼠中，除了组织学侵蚀外，还观察到后爪体积、滑膜组织中细胞因子mRNA表达和Glu水平显著增加。在从这些关节炎大鼠制备的培养的滑膜成纤维细胞中，[H-3]Glu积累急剧增加，其生化和药理学特征与正常滑膜成纤维细胞中观察到的相似。暴露于500 μ M的Glu使关节炎大鼠而非正常大鼠的培养的滑膜成纤维细胞中5-溴-2 '-脱氧尿苷的掺入加倍，而不显著影响两种滑膜成纤维细胞中不同细胞因子的mRNA表达。这些结果表明，谷氨酸可能至少部分发挥作用的机制与细胞增殖，通过特定的功能性表达的滑膜在类风湿性关节炎。(c)2005年爱思唯尔公司All rights reserved.
Although previous studies have demonstrated increased levels of the brain neurotransmitter glutamate (Glu) in the synovial fluid from patients with arthritis, not much attention has been paid to the possible role of Glu in joint synovial tissues to date. Constitutive expression of mRNA was for the first time shown with glutamate aspartate transporter, glutamate transporter-1 and excitatory amino acid carrier-1 (EAAC1), in addition to with particular ionotropic and metabotropic Gin receptors, in cultured synovial fibroblasts prepared from knee joints of male Lewis rats. Immunohistochemical analysis revealed high localization of immunoreactive EAAC1 at synovial tissues. The accumulation of [H-3]Glu occurred in a temperature- and sodium-dependent manner in cultured synovial fibroblasts, with a Km of 23.1 +/- 1.1 mu M and a V-max of 237.1 +/- 31.1 pmol(mg protein min), respectively. In rats with arthritis induced by immunization to type-II collagen, marked increases were seen in hind paw volume, cytokine mRNA expression and Glu levels in synovial tissues, in addition to histological erosion. In cultured synovial fibroblasts prepared from these arthritic rats, [H-3]Glu accumulation was drastically increased with biochemical and pharmacological profiles similar to those seen in normal synovial fibroblasts. The exposure to Glu at 500 mu M doubled the incorporation of 5-bromo-2'-deoxyuridine in cultured synovial fibroblasts of arthritic but not normal rats, without significantly affecting mRNA expression of different cytokines in both synovial fibroblasts. These results suggest that Glu may at least in part play a role in mechanisms associated with cellular proliferation through particular transporters functionally expressed by synovium in rheumatoid arthritis. (c) 2005 Elsevier Inc. All rights reserved.