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卡泊三醇和倍他米松二丙酸酯对角质促成细胞增生性皮炎诱导的小鼠银屑病样皮炎具有不同的免疫调节作用。

Calcipotriol and betamethasone dipropionate exhibit different immunomodulatory effects on imiquimod-induced murine psoriasiform dermatitis.

机构信息

Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.

出版信息

J Dermatol. 2020 Feb;47(2):155-162. doi: 10.1111/1346-8138.15155. Epub 2019 Nov 24.

Abstract

Psoriasis is a T-helper (Th)1/Th17-mediated, chronic inflammatory dermatitis that is commonly treated with topical corticosteroids and vitamin D analogs. The combination of a topical corticosteroid and vitamin D analog showed superior efficacy to each alone in clinical trials; however, the mechanisms by which the topical corticosteroid and vitamin D analog exert their effects on lesional skin in combination and each alone remain unknown. In this study, we examined the effects of combined calcipotriol (Cal)/betamethasone dipropionate (BD) ointment on psoriasis in vivo, utilizing imiquimod (IMQ)-induced murine psoriasiform skin inflammation, compared with each alone. Vehicle, Cal/BD, Cal or BD was applied on the shaved back skin for 3 consecutive days. Then, IMQ was applied for 6 consecutive days. Twenty-four hours after the last IMQ treatment, the murine skin was evaluated clinically and pathologically. mRNA expressions were examined by quantitative polymerase chain reaction. All ointments alleviated IMQ-induced psoriasiform skin inflammation clinically in comparison with vehicle application. Cal/BD suppressed mRNA expressions of cytokines involved in psoriasis pathogenesis such as interleukin (IL)-17A and IL-22 efficiently. Cal alone induced IL-10 expression, whereas BD alone reduced IL-6 mRNA expression and the number of phosphorylated signal transducer and activator of transcription 3-positive cells in lesional skin. Our study revealed that Cal and BD have different effects on IMQ-induced psoriasiform skin. Some of the immune effects of Cal and BD may be additive or synergistic, which may account for the superior clinical efficacy of their combination.

摘要

银屑病是一种由辅助性 T 细胞 (Th)1/Th17 介导的慢性炎症性皮肤病,通常采用局部皮质类固醇和维生素 D 类似物治疗。在临床试验中,局部皮质类固醇和维生素 D 类似物联合应用的疗效优于单独使用,然而,联合应用和单独应用时局部皮质类固醇和维生素 D 类似物对皮损皮肤的作用机制尚不清楚。在这项研究中,我们利用咪喹莫特 (IMQ) 诱导的小鼠银屑病样皮肤炎症,研究了卡泊三醇 (Cal)/倍他米松二丙酸酯 (BD) 软膏联合应用对银屑病的体内作用,与单独应用进行了比较。剃光的背部皮肤连续 3 天分别涂抹载体、Cal/BD、Cal 或 BD,然后连续 6 天涂抹 IMQ。最后一次 IMQ 处理后 24 小时,对小鼠皮肤进行临床和病理评估。通过定量聚合酶链反应检测 mRNA 表达。与载体应用相比,所有软膏均可明显缓解 IMQ 诱导的银屑病样皮肤炎症。Cal/BD 可有效抑制与银屑病发病机制相关的细胞因子如白细胞介素 (IL)-17A 和 IL-22 的 mRNA 表达。Cal 单独诱导 IL-10 表达,而 BD 单独降低 IL-6 mRNA 表达和磷酸化信号转导和转录激活因子 3 阳性细胞在皮损皮肤中的数量。我们的研究表明,Cal 和 BD 对 IMQ 诱导的银屑病样皮肤有不同的作用。Cal 和 BD 的一些免疫作用可能具有相加或协同作用,这可能是它们联合应用的临床疗效优于单独应用的原因。

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