Regulatory mechanisms of neuro-endocine-immune system in the skin

最近，日本患有过敏性疾病，特别是特应性皮炎的患者数量不断增加。皮肤屏障功能障碍、血清IgE升高转向Th2免疫反应以及对精神和/或身体应激的异常反应被认为是重要的病因和加重因素。众所周知，引起发炎皮肤瘙痒的介质是组胺、前列腺素和速激素。其中，P物质（SP）在调节外周瘙痒感觉中起核心作用。我们最近发现SP可以从表皮角质形成细胞或成纤维细胞中释放。为了阐明应激对Th2变应性炎症的影响，我们在知情同意的情况下，研究了SP、组胺对il - 4诱导的Th2趋化因子的影响，尤其是来自特应性皮炎皮损的成纤维细胞产生eotaxin的影响。我们观察到SP和组胺在IL-4刺激下协同增加eotaxin的产生和mRNA的表达。我们还通过RT-PCR和FAGS分析证明，IL-4和SP和/或组胺刺激成纤维细胞的IL-4受体表达比单独IL-4刺激的成纤维细胞表达增加。在ad源性成纤维细胞中，与正常对照相比，SP或组胺对il - 4- r表达的提高明显更高，并持续到传代9。这种异常现象是先天的还是后天的，在本项目中没有明确。皮肤驻留细胞在AD中通过向Th2免疫反应的转变提供了一些重要的作用。IL-4R、NK1-R或H1/H2R基因的多态性及其与Th2血红素生成加速的关系应在未来的订制药物工作中进一步研究。

The number of patients suffering allergic diseases, especially atopic dermatitis has been increasing in recent Japan. Dysfunction of skin barrier, shift to Th2 immune response with elevated serum IgE and abnormal response to mental and/or physical stress are thought to be important etiological and exacerbating factors. It was well known that mediators causing itch in inflamed skin is histamine, prostaglandin and tachykinins. Among these, substance P (SP) plays central role to mediate peripheral itch sensation. We have recently found that SP can be released from epidermal keratinocytes or fibroblasts. To clarify stress response on Th2 allergic inflammations, we conducted the effect of SP, histamine on IL4-induced Th2 chemokines, especially eotaxin production by fibroblasts derived from skin lesions of atopic dermatitis under informed consent.We observed that SP and histamine increased synergistically eotaxin production and mRNA expression when stimulated with IL-4. We also proved that the expression of IL-4 receptor in fibroblasts stimulated with IL-4 and SP and /or histamine was increased rather than stimulated with IL-4 alone by RT-PCR and FAGS analysis.This elevated IL4-R expression by SP or histamine was significantly higher and persisted to passage 9 in AD-derived fibroblasts than in normal controls. Whether this aberrant phenomenon was intrinsic or acquired in AD is not clarified in this project. The skin residents cells provide some important roles through the shift to Th2 immune response in AD. Polymorphisms of IL-4R, NK1-R, or H1/H2R genes and their relationship to accerelated Th2 ehemokine production should be studied in the future work for the order made medicine in the future.