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Analysis of function of fibroblast derived from atopic dermatitis and skin remodeling

特应性皮炎成纤维细胞功能分析与皮肤重塑

基本信息

批准号：
13670891
负责人：
BAE SangJae
金额：
$ 0.9万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670891/
关键词：
eotaxin fibroblast atopic dermatitis substance P histamine TGF β IL-4 neutral endopeptidase Atopic dermatitis Eotaxin Fibroblast Substance P Histamine TGFβ

项目摘要

Eotaxin plays a central role in the development of allergic disease, including atopic dermatitis (AD), asthma, and nasal allergy, because it acts as chemoattractant for eosinophils in allergic inflammation. In this study, we confirmed that eotaxin and its mRNA expression were increased in the skin of AD patients compared with that of healthy volunteers using immunohistochemical methods and the reverse-transcriptase polymerase chain reaction (RT-PCR). It was reported that the inflammatory cytokines interleukin-4 (IL-4), tumor necrosis factor-α, and interleukin-13 synergistically enhance eotaxin production in normal human fibroblasts. Histamine and substance P (SP) are known to be important mediators of allergic inflammation. We reported that not only SP but also histamine induces eotaxin production by cultured human fibroblasts.In addition, we showed that TGF β synergistically induce eotaxin production in presence of IL-4 stimulus. Next, we investigated that eotaxin production pattern of fibroblasts derived from atopic dermatitis (AD) and healthy controls with IL-4 stimulus. As results, eotaxin production was higher in AD fibroblasts rather than healthy control.Finally, we reported NEP (neutral endopeptidase) was induced in dermal fibroblast when stimululated with SP. These observations suggest that dermal fibroblasts have an important role in allergic inflammation via eotaxin production and skin remodelling.

嗜酸性粒细胞趋化因子在变应性疾病（包括特应性皮炎（AD）、哮喘和鼻变态反应）的发展中起核心作用，因为其在变应性炎症中充当嗜酸性粒细胞的化学引诱物。在这项研究中，我们证实，嗜酸性粒细胞趋化因子及其mRNA的表达增加，在AD患者的皮肤与健康志愿者相比，使用免疫组化方法和逆转录聚合酶链反应（RT-PCR）。据报道，炎性细胞因子白细胞介素-4（IL-4）、肿瘤坏死因子-α和白细胞介素-13协同增强正常人成纤维细胞中的嗜酸性粒细胞趋化因子产生。组胺和P物质（SP）是过敏性炎症的重要介质。我们报道了SP和组胺都能诱导培养的人成纤维细胞产生eotaxin，此外，我们还发现TGF β在IL-4刺激下协同诱导eotaxin的产生。接下来，我们研究了用IL-4刺激来源于特应性皮炎（AD）和健康对照的成纤维细胞的嗜酸细胞活化趋化因子产生模式。最后，我们报道了当SP刺激皮肤成纤维细胞时，皮肤成纤维细胞中的中性内肽酶（neutral endopeptidase，NEP）被诱导。这些观察结果表明，皮肤成纤维细胞通过产生eotaxin和皮肤重塑在变应性炎症中起重要作用。