Analysis of role of aryl hydrocarbon receptor for pathophysiology of atopic dermatitis

为了阐明特应性皮炎的致炎机制，我重点研究了芳烃受体(AhR)信号转导途径。在最近的研究中，Tauchi M等人。研究表明，角质形成细胞中芳烃受体的结构性表达会导致转基因小鼠特应性皮炎样皮肤病变。他们的发现非常耐人寻味，因为角质形成细胞分泌的物质会引起皮肤炎症。他们的皮肤炎症就像特应性皮炎。利用已建立的转基因小鼠模型和AhR高表达培养的角质形成细胞，寻找在AhR激活下诱导的候选细胞。因此，我发现一些促炎细胞因子的表达增加，这可能与特应性皮炎有关。我观察到在加入AhR激活剂后，培养的角质形成细胞中它们的表达增加。这些结果提示，AhR的激活诱导了角质形成细胞中一些致炎细胞因子的表达。在特应性皮炎中，树突状细胞在炎症的建立中具有重要作用。我推测角质形成细胞中AhR的激活可以诱导树突状细胞的活性。

To elucidate the mechanism how to induce inflammation in atopic dermatitis, I focused aryl hydrocarbon receptor (AhR) signaling pathway. In the recent study, Tauchi M et al. showed that constitutive expression of aryl hydrocarbon receptor in keratinocytes causes atopic dermatitis-like skin lesions in transgenic mouse.Their discovery is very intriguing because secretion production by keratinocyte cause skin inflammation. And their skin inflammation is like atopic dermatitis. I seeked candidates which are induced under AhR activation by using previous transgenic mouse model and AhR-overexpressed cultured keratinocyte. So I identified increasing expression of some proinflammatory cytokines, which may be related in atopic-like dermatitis. I observed increase expression of them in culutured keratinocyte after the addition of AhR activator. These data suggest that AhR activation induced expression of some proinflammatory cytokines in keratinocyte.In atopic dermatitis, dendritic cell has a significant role in establishment of inflamation. I speculate that AhR activation in keratinocyte induce dendritic cell activity.