Genetic analysis of stress effects on cutaneous immune system

虽然压力被认为会加重炎症疾病，但其机制尚不清楚。因此，以BALB / c雄性小鼠为实验对象，观察长期隔离对小鼠接触性皮炎（CS）及朗格汉斯细胞（LC）、角质形成细胞（KC）功能的影响。结果表明，慢性应激可使LC的CS反应和抗原提呈能力显著增强，而KC的抗原提呈能力、IL-1-α和TNF-α（炎性细胞因子）的产生和增殖活性显著降低。然后，提取来自隔离应激小鼠的KC的RNA，并使用RT-PCR方法分析各种基因的mRNA表达。作为初步实验，分析了用苯酚（一种主要刺激物）和三硝基氯苯（TNCB）（一种接触致敏剂）刺激后KC的mRNA表达。结果表明，前者仅诱导ICAM-1 mRNA的表达，而后者可诱导ICAM-1、E-cadherin（粘附分子）、转氨酶（分化标志物）、c-fos和c-myc（即早基因）、促肾上腺皮质激素释放激素受体和P物质受体（神经递质相关）、IL-1-α和TNF-α的mRNA的显著表达。慢性应激瞬时上调这些mRNA。而TNCB对慢性应激小鼠的作用，仅KC的转氨酶和P物质受体mRNA表达增加，其他种类的mRNA表达降低。提示慢性应激可使LC功能增强，KC功能和分化受损，神经纤维释放P物质与这些调节有关。

Although stress is thought to worsen inflammation diseases, the mechanism is not known. Therefore, long period of isolation was administered to BALB / c male mouse as chronic mental stress, and the influence on contact dermatitis (CS) and function of Langerhans cells (LC) and keratinocytes (KC) were analyzed. As a result, by chronic stress the CS responses and the antigen presenting ability of LC were markedly enhanced, while the antigen presenting ability, IL-1-α and TNF-α (inflammatory cytokine) production and proliferative activity of KC were drastically reduced. Then, RNA of KC from mice received isolation stress was extracted and mRNA expression for various genes was analyzed using RT-PCR method. As preliminary experiments mRNA expression by KC after stimulation with phenol, a primary irritant, and trinitrochlorobenzene (TNCB), a contact sensitizer, were analyzed. As a result, only adhesion molecule ICAM-1 mRNA expression was induced by the former, while marked expression of mRNA for ICAM-1, E-cadherin (adhesion molecule), transglutaminase (differentiation marker), c-fos and c-myc (immediate early genes), corticotrophin releasing hormone receptor and substance P receptor ( neurotransmitter related), and IL-1-α and TNF-α were observed by the latter. Chronic stress up-regulated these mRNA transiently. However, application of TNCB to chronically stressed mouse, only expression of mRNA for transglutaminase and substance P receptor by KC was increase, and mRNA expression for other genre was reduced compared to control. These results suggested that by chronic stress the function of LC is enhanced, while function and differentiation of KC are impaired and that substance P released from neurofibers is related to these modulations.