Effects of the mutant cytokine therapy in atopic dermatitis

为了在肥大细胞中表达细胞因子DNA，将连接到肥大细胞特异性启动子的IL-4注射到小鼠卵子中。新生小鼠及其子代未检测到明显的IL-4转移。因此，我们将转基因系统表达突变型IL-4的策略转变为免疫小鼠。通过连续局部应用半抗原建立了Th2型慢性皮炎小鼠。用编码IL-4的DNA疫苗、显性-负性诱骗IL-4或显性-负性诱骗IL-4/IL-13治疗小鼠。IL-4/IL-13诱骗疫苗能有效抑制Th2型皮炎，IL-4诱骗疫苗对Th2型皮炎抑制作用有限。IL-4激动剂或模拟FNA均无作用。本实验揭示了显性负性IL-4/IL-13诱骗DNA是一种治疗特应性皮炎的有效工具。为了评估模型小鼠的瘙痒感觉，我们建立了声学分析的抓挠运动测量系统。该系统宣布了特应性皮炎(AD)模型小鼠不可见的快速抓挠行为。为了了解肥大细胞在AD中的作用，研究了肥大细胞衍生的酶在细胞因子激活中的作用。人肥大细胞糜酶成功地作用于IL-18，并产生了一个活性物种。这揭示了肥大细胞及其乳糜酶分泌在AD皮损中的重要性。

To express cytokine DNA in mast cells, IL-4 ligated to a mast cell specific promoter was injected to mouse eggs. No obvious transferred IL-4 was detected in the born mice and their offspring. Therefore, we switched strategy to express mutant IL-4 species by transgenic system to vaccination to mouse.Mice with Th2 type chronic dermatitis were established with serially topical application of hapten. These mice were treated with DNA vaccine coding IL-4, dominant-negative decoy IL-4 or dominant-negative decoy IL-4/IL-13. Th2 type dermatitis was successfully suppressed dominant negative IL-4/IL-13 decoy vaccination, and limited effects with IL-4 decoy. IL-4 agonist or mock FNA showed no effects. This experiment revealed dominant-negative IL-4/IL-13 decoy DNA is a potent therapeutic tool for atopic dermatitis.To evaluate the itching sensation of model mouse, we established a measuring system of scratching movement by acoustic analysis.This system declared invisibly rapid scratching behavior of the atopic dermatitis (AD) model mouse. Then, this system revealed effective suppression of the scratching counts of AD mouse with oral administration of anti-histamine dose dependently.To know the roles of mast cells in AD, the mast cell derived enzymes were evaluated in cytokine activation. The human mast cell chymase processed IL-18 successfully and generated an active species. This revealed importance of mast cells and their chymase discharge in AD skin lesions.