Genetic analysis of stress effects on cutaneous immune system

应激对皮肤免疫系统影响的遗传分析

• 批准号: 10670377
• 负责人: NAKANO Yumiko
• 金额: $ 1.98万
• 依托单位: Osaka Prefectural Institute of Public Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670377/
• 关键词: Stress; Contact sensitivity; Langerhans cell; Keratinocyte; isolation; adhesion molecule; cytokine; neuropeptide; 慢性的精神的ストレス; 遺伝子発現解析; RT-PCR法; アレルギー性接触皮膚炎; 単独隔離; 接着分子; サイトカイン; 神経ペプチド

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.

尽管压力被认为会加重炎症性疾病，但其机制尚不清楚。因此，将长期隔离的BALB/c雄性小鼠作为慢性心理应激，分析其对接触性皮炎(CS)及郎格罕斯细胞(LC)和角质形成细胞(KC)功能的影响。结果表明，慢性应激使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和肿瘤坏死因子-α(炎性细胞因子)的产生及增殖活性显著降低。然后提取隔离应激小鼠KC的RNA，用RT-PCR方法分析各基因的表达。作为初步实验，分析了主要刺激物苯酚和接触增敏剂三硝基氯苯(TNCB)刺激后KC的mRNA表达。结果表明，前者仅诱导黏附分子ICAM-1mRNA表达，而后者则明显表达ICAM-1、E-钙粘素(黏附分子)、转谷氨酰胺酶(分化标记物)、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和肿瘤坏死因子-α。慢性应激会短暂上调这些信使核糖核酸。然而，在慢性应激小鼠中，仅KC的转谷氨酰胺酶和P物质受体的mRNA表达较对照组增加，其他类型的mRNA的表达与对照组相比降低。这些结果提示，慢性应激使LC功能增强，KC功能和分化功能受损，神经纤维释放P物质与这些调节有关。

项目成果

Nakano Y.: "Antigen-presenting cell function of epidermal cells activated by hapten application"Brit J Dermatol. 38. 786-794 (1998)

Nakano Y.：“通过半抗原应用激活表皮细胞的抗原呈递细胞功能”Brit J Dermatol。

Nakano Y. and Nishimura H.: "Effect of isolation stress on cutaneous immune function"J Immunol.. (in press).

Nakano Y. 和 Nishimura H.：“隔离压力对皮肤免疫功能的影响”《免疫学杂志》（出版中）。

Y.Nakano et al: "Immune function and lifestyle of taxi drivers in Japan" Industrial Health. 36. 32-39 (1998)

Y.Nakano 等：“日本出租车司机的免疫功能和生活方式”工业健康。

中野ユミ子: "ストレスは接触皮膚炎を増悪する"臨床免疫. 32. 365-371 (1999)

Yumiko Nakano：“压力使接触性皮炎恶化”《临床免疫学》32. 365-371 (1999)。

Nakano Y., Nakamura S., Hirata M., Harada K., Ando K., Tabuchi T., Matunaga I. and Oda H.: "Immune function and lifestyle of taxi drivers."Industrial Health. 36. 32-39 (1998)

Nakano Y.、Nakamura S.、Hirata M.、Harada K.、Ando K.、Tabuchi T.、Matunaga I. 和 Oda H.：“出租车司机的免疫功能和生活方式。”工业健康。