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局部应用葡萄糖可诱导特应性皮炎小鼠模型及角质形成细胞培养中的紧密连接蛋白-1和丝聚合蛋白表达,通过修复皮肤屏障功能发挥抗炎作用。

Topical Glucose Induces Claudin-1 and Filaggrin Expression in a Mouse Model of Atopic Dermatitis and in Keratinocyte Culture, Exerting Anti-inflammatory Effects by Repairing Skin Barrier Function.

作者信息

Yamada Kiyoko, Matsushita Kenji, Wang Jingshu, Kanekura Takuro

机构信息

Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, 890-8520 Kagoshima, Japan.

出版信息

Acta Derm Venereol. 2018 Jan 12;98(1):19-25. doi: 10.2340/00015555-2807.

DOI:10.2340/00015555-2807
PMID:28967978
Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Corticosteroids, which are widely used for AD treatment, have adverse effects, and alternative treatments are urgently needed. This study examined the effect of topical application of high-dose glucose on inflamed skin in a murine model of AD. High-dose glucose treatment on the ear reduced dermatitis scores and ear thicknesses in mite antigen-treated NC/Nga mice. The levels of thymus and activation-regulated chemokine (TARC), Th cytokines (interleukin (IL)-4, IL-5, IL-12, IL-13, and (interferon) IFN-γ), and IgE were decreased in the serum of high-dose glucose-treated mice. Expression of claudin-1 and filaggrin was reduced in the ear epithelium in the NC/Nga mice. However, the reduced expression was restored by topical treatment with high-dose glucose. High-dose glucose also induced the expression of claudin-1 and filaggrin in cultured human skin keratinocytes. Co-stimulation with IL-4, IL-13, and thymic stromal lymphoprotein downregulated the expression of filaggrin in culture. However, high-dose glucose treatment restored the reduced expression of filaggrin. These results suggest that high-dose glucose treatment suppresses inflammation in the skin lesions by improving the skin barrier function.

摘要

特应性皮炎(AD)是一种慢性炎症性皮肤病。广泛用于AD治疗的皮质类固醇有不良反应,因此迫切需要替代治疗方法。本研究在AD小鼠模型中检测了局部应用高剂量葡萄糖对炎症皮肤的影响。在经螨抗原处理的NC/Nga小鼠耳部进行高剂量葡萄糖治疗可降低皮炎评分和耳部厚度。高剂量葡萄糖治疗小鼠血清中的胸腺和活化调节趋化因子(TARC)、Th细胞因子(白细胞介素(IL)-4、IL-5、IL-12、IL-13和干扰素(IFN)-γ)以及IgE水平降低。NC/Nga小鼠耳部上皮中claudin-1和丝聚合蛋白的表达减少。然而,通过高剂量葡萄糖局部治疗可恢复其降低的表达。高剂量葡萄糖还可诱导培养的人皮肤角质形成细胞中claudin-1和丝聚合蛋白的表达。IL-4、IL-13和胸腺基质淋巴细胞生成素共同刺激可下调培养物中丝聚合蛋白的表达。然而,高剂量葡萄糖治疗可恢复丝聚合蛋白降低的表达。这些结果表明,高剂量葡萄糖治疗可通过改善皮肤屏障功能来抑制皮肤病变中的炎症。

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