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

• 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

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过敏性疾病（包括特应性皮炎 (AD)、哮喘和鼻过敏）的发展中起着核心作用，因为它在过敏性炎症中充当嗜酸性粒细胞的趋化剂。在这项研究中，我们证实嗜酸性粒细胞趋化因子及其 mRNA 表达增加。据报道，使用免疫组织化学方法和逆转录酶聚合酶链反应（RT-PCR）与AD患者皮肤中的炎症细胞因子白细胞介素4进行比较。 (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嗜酸细胞活化趋化因子的产生。我们报道，组胺和 P 物质 (SP) 不仅是过敏性炎症的重要介质。组胺诱导培养的人成纤维细胞产生嗜酸细胞趋化因子。此外，我们发现 TGF β 在 IL-4 刺激存在下协同诱导嗜酸细胞趋化因子的产生。研究了来自特应性皮炎 (AD) 的成纤维细胞和健康对照组在 IL-4 刺激下的嗜酸细胞趋化因子的产生模式，结果显示，AD 成纤维细胞中嗜酸细胞趋化因子的产生高于健康对照。最后，我们报道了在 IL-4 刺激下诱导了 NEP（中性内肽酶）。这些观察结果表明，真皮成纤维细胞通过嗜酸细胞趋化因子的产生和皮肤在过敏性炎症中发挥重要作用。重塑。

项目成果

Bace Sangae: "Inhibitory effect of cetirizine of histamine-induced eotaxin production."Curr Ther Res Clin Exp.

Bace Sangae：“西替利嗪对组胺诱导的嗜酸细胞趋化因子产生的抑制作用。”Curr Ther Res Clin Exp。

Bae SangJae, et al.: "Substance P induced preprotachykinin-A mRNA, meutron peptidase mRNA and substance P in cultured normal fibroblasts"Int Arch Allergy Immunol.. 127. 316-321 (2002)

Bae SangJae 等：“在培养的正常成纤维细胞中 P 物质诱导前速激肽-A mRNA、中子肽酶 mRNA 和 P 物质”Int Arch Allergy Immunol.. 127. 316-321 (2002)

Kazuhiro Shimizu, et al.: "The induction of Heme oxygenase-1 by exogenous nitric oxide in ex vivo normal human skin"J Dermatology. 30・1. 17-25 (2003)

Kazuhiro Shimizu 等：“体外正常人皮肤中外源性一氧化氮的诱导”J Dermatology 30・1 (2003)。

Bae SangJae, et al.: "Inhibitory effect of epinastine chloride on histamine-induced eotaxin production in normal human fibroblasts"Jpn Phamacol Ther. 30・2. 97-102 (2002)

Bae SangJae等：“氯化依匹斯汀对正常人成纤维细胞中组胺诱导的嗜酸细胞趋化因子产生的抑制作用”Jpn Phamacol Ther 97-102(2002)。

Katayama Ichiro: "Stress response, tachykinin, and cutaneous inflammation."J Investig Dermatol Symp Proc. 6・1. 81-86 (2001)

片山一郎：“应激反应、速激肽和皮肤炎症。”J Investig Dermatol Symp Proc. 6・1 (2001)。