Reduced susceptibility to collagen-induced arthritis in DBA/1J mice expressing the TSG-6 transgene
Reduced susceptibility to collagen-induced arthritis in DBA/1J mice expressing the TSG-6 transgene
复制标题
DOI：
10.1002/art.10503
复制
发表时间：
2002-09-01
影响因子：
--
通讯作者：
Wisniewski, HG
中科院分区：
文献类型：
--
作者：
Mindrescu, C;Dias, AAM;Wisniewski, HG
目标。促炎因子可诱导TSG-6（肿瘤坏死因子刺激基因6）的表达。本研究旨在观察TSG-6转基因小鼠在胶原诱导关节炎（CIA）模型中关节局部表达的影响。我们在T细胞特异性缺失启动子的控制下产生了含有TSG-6基因的转基因小鼠。用牛II型胶原蛋白（CII）免疫诱导关节炎，并根据关节炎发病率、关节炎指数和足垫肿胀监测其进展。采用酶联免疫吸附法测定抗cii抗体和细胞因子的产生。采用基因表达阵列比较转基因小鼠和对照小鼠在cia不同阶段的基因表达谱。经CII免疫后，TSG-6在转基因小鼠的肢体中有表达，而在非转基因动物中的表达不显著。TSG-6转基因动物CIA发生率降低，发病延迟，临床关节炎各项指标均显著降低。然而，TSG-6转基因小鼠对CII的免疫反应未被明显抑制。TSG-6表达已在类风湿和其他形式的关节炎患者中得到证实。我们的数据表明，在小鼠自身免疫性关节炎模型中，炎症部位局部表达TSG-6可有效抑制炎症和关节破坏。因此，TSG-6可能在人类类风湿关节炎及相关疾病中发挥类似的调节作用，并可能具有治疗人类自身免疫性关节炎的潜力。
Objective. Expression of TSG-6 (tumor necrosis factor-stimulated gene 6) is induced by proinflammatory cytokines. This study was undertaken to examine the effects of local expression of TSG-6 in arthritic joints of TSG-6 transgenic mice, in the collagen-induced arthritis (CIA) model.Methods. We generated transgenic mice that harbored the TSG-6 gene under the control of the T cell-specific lck promoter. Arthritis was induced by immunization with bovine type II collagen (CII), and its progression was monitored based on the incidence of arthritis, the arthritis index, and footpad swelling. Anti-CII antibodies and cytokine production were determined by enzyme-linked immunosorbent assay. Gene expression arrays were used to compare gene expression profiles of transgenic and control mice at various stages of CIA.Results. TSG-6 was expressed in limbs of transgenic mice after immunization with CII, while its expression in nontransgenic animals was insignificant. The incidence of CIA was reduced in TSG-6 transgenic animals, its onset delayed, and all parameters of clinical arthritis significantly reduced. However, the immune response against CII was not significantly inhibited in TSG-6 transgenic mice.Conclusion. TSG-6 expression has been demonstrated in patients with rheumatoid and other forms of arthritis. Our data show that local expression of TSG-6 at sites of inflammation results in potent inhibition of inflammation and joint destruction in a model of autoimmune arthritis in mice. Therefore, it is likely that TSG-6 plays a similar modulatory role in human rheumatoid arthritis and related diseases and may have potential for the treatment of autoimmune arthritis in humans.