Genetic analysis of stress effects on cutaneous immune system

尽管人们认为压力会加重炎症性疾病，但其机制尚不清楚。为此，采用长期分离BALB / c雄性小鼠作为慢性精神应激，分析其对接触性皮炎（CS）及朗格汉斯细胞（LC）和角化细胞（KC）功能的影响。结果表明，慢性应激显著增强了LC的CS应答和抗原呈递能力，而KC的抗原呈递能力、IL-1-α和TNF-α（炎性细胞因子）的产生和增殖活性均显著降低。然后提取分离应激小鼠KC的RNA，采用RT-PCR方法分析各基因mRNA的表达情况。作为初步实验，我们分析了初级刺激物苯酚和接触致敏剂三硝基苯（TNCB）刺激后KC mRNA的表达。结果，前者只诱导粘附分子ICAM-1 mRNA表达，而后者可诱导ICAM-1、粘附分子E-cadherin、分化标志物转谷氨酰胺酶、即时早期基因c-fos和c-myc、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 mRNA表达。慢性应激可短暂上调这些mRNA。而长期应激小鼠经TNCB处理后，仅KC中谷氨酰胺转肽类酶和P物质受体mRNA表达量增加，其他类型mRNA表达量均较对照降低。这些结果表明，慢性应激使LC功能增强，而KC的功能和分化受到损害，神经纤维释放的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.