Curative effects of CpG DNA administration on scleroderma-like syndrome of Tsk/+mice

CpG DNA给药对Tsk/小鼠硬皮病样综合征的疗效

• 批准号: 13670466
• 负责人: ICHINO Motohide
• 金额: $ 0.96万
• 依托单位: Yokohama City University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670466/
• 关键词: CpG DNA; Scleroderma; Tsk; + mice; Th1; Th2; Autoimmune disease; CpG DNA

The tight-skin (Tsk/+) mice spontaneously develop scleroderma-like disease characterized by cutaneous hyperplasia, auto antibodies and pulmonary emphysema. IL-4, a typical Th2 cytokine, has been suggested to play an important role in the pathogenesis.Here, we examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducer of Th1 cytokines, to prevent the development of scleroderma-like syndrome of Tdk/+mice. After 7 times administration of CpG ODN with 3-wk interval into 1-wk old Tsk/+ mice, dermal fibrosis was significantly reduced and low levels of serum antinuclear antibodies were detected. Furthermore, CpG ODN had a long-term inhibitory effect on the development of skin fibroses. IFN-γ producing cells induced by CpG ODN administration might contribute to inhibit the development of skin thickness.However, no curative effect was observed on lung emphysema. The mechanisms of emphysema development could be independent of Th1/Th2 cytokine balance. When CpG ODN administration was started with 6-wk old Tsk/+ mice, the pathogenesis of the disease was not improved.Theses results indicate that a Th1-biased cytokine milieu induced by CpG ODN ameliorate scleroderma-like syndrome, and support that CpG ODN treatment may be a feasible approach in the therapy of Th2-driven diseases.

紧皮肤（Tsk/+）小鼠自发地出现以皮肤增生、自身抗体和肺气肿为特征的硬皮病样疾病，IL-4（一种典型的 Th2 细胞因子）被认为在发病机制中发挥着重要作用。我们检查了非甲基化 CpG 寡脱氧核苷酸 (ODN) 的能力，它是 Th1 细胞因子的有效诱导剂，可预防硬皮病样综合征的发生Tdk/+小鼠在1周龄Tsk/+小鼠中间隔3周给予CpG ODN 7次后，真皮纤维化显着减少，并且检测到低水平的血清抗核抗体。此外，CpG ODN具有长效。对CpG ODN施用诱导的产生IFN-γ的细胞的发展的长期抑制作用可能有助于抑制皮肤厚度的发展。然而，没有观察到对皮肤纤维化的疗效。肺气肿发生的机制可能与 Th1/Th2 细胞因子平衡无关。当开始对 6 周大的 Tsk/+ 小鼠施用 CpG ODN 时，该疾病的发病机制并未得到改善。这些结果表明 Th1- CpG ODN 诱导的偏向细胞因子环境可改善硬皮病样综合征，并支持 CpG ODN 治疗可能是治疗 Th2 驱动疾病的可行方法。