Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
J Dermatol Sci. 2013 Sep;71(3):174-83. doi: 10.1016/j.jdermsci.2013.04.023. Epub 2013 May 2.
Thymic stromal lymphopoietin (TSLP) is produced by epidermal keratinocytes, and it induces Th2-mediated inflammation. TSLP expression is enhanced in lesions with atopic dermatitis, and is a therapeutic target. Antimycotic agents improve the symptoms of atopic dermatitis.
The objective of this study was to examine whether antimycotics suppress TSLP expression in human keratinocytes.
Normal human keratinocytes were incubated with polyinosinic-polycytidylic acid (poly I:C) plus IL-4 in the presence of antimycotics. TSLP expression was analyzed by ELISA and real time PCR. Luciferase assays were performed to analyze NF-κB activity. IκBα degradation was analyzed by Western blot analysis.
Poly I:C plus IL-4 increased the secretion and mRNA levels of TSLP, which was suppressed by an NF-κB inhibitor, and also enhanced NF-κB transcriptional activities and induced the degradation of IκBα in keratinocytes. The antimycotics itraconazole, ketoconazole, luliconazole, terbinafine, butenafine, and amorolfine suppressed the secretion and mRNA expression of TSLP, NF-κB activity, and IκBα degradation induced by poly I:C plus IL-4. These suppressive effects were similarly manifested by 15-deoxy-Δ-(12,14)-PGJ2 (15d-PGJ2), a prostaglandin D2 metabolite. Antimycotics increased the release of 15d-PGJ2 from keratinocytes and decreased the release of thromboxane B2, a thromboxane A2 metabolite. Antimycotic-induced suppression of TSLP production and NF-κB activity was counteracted by an inhibitor of lipocalin type-prostaglandin D synthase.
Antimycotics itraconazole, ketoconazole, luliconazole, terbinafine, butenafine, and amorolfine may suppress poly I:C plus IL-4-induced production of TSLP by inhibiting NF-κB via increasing 15d-PGJ2 production in keratinocytes. These antimycotics may block the overexpression of TSLP in lesions with atopic dermatitis.
胸腺基质淋巴细胞生成素（TSLP）由表皮角质形成细胞产生，并诱导 Th2 介导的炎症。特应性皮炎皮损中 TSLP 表达增强，是治疗靶点。抗真菌药物可改善特应性皮炎症状。
本研究旨在探讨抗真菌药物是否抑制人角质形成细胞中 TSLP 的表达。
在存在抗真菌药物的情况下，用聚肌苷酸-聚胞苷酸（poly I:C）加白细胞介素-4（IL-4）孵育正常人角质形成细胞。通过 ELISA 和实时 PCR 分析 TSLP 表达。进行荧光素酶测定分析 NF-κB 活性。通过 Western blot 分析分析 IκBα 降解。
poly I:C 加 IL-4 增加了 TSLP 的分泌和 mRNA 水平，NF-κB 抑制剂可抑制该水平，还增强了角质形成细胞中 NF-κB 转录活性并诱导 IκBα 降解。酮康唑、克霉唑、卢立康唑、特比萘芬、布替萘芬和阿莫罗芬等抗真菌药物抑制了 poly I:C 加 IL-4 诱导的 TSLP 分泌和 mRNA 表达、NF-κB 活性和 IκBα 降解。15-脱氧-Δ-（12,14）-PGJ2（15d-PGJ2）是前列腺素 D2 代谢物，其表现出相似的抑制作用。抗真菌药物增加了角质形成细胞中 15d-PGJ2 的释放，并减少了血栓烷 B2（血栓烷 A2 代谢物）的释放。脂氧素型前列腺素 D 合酶抑制剂可拮抗抗真菌药物诱导的 TSLP 产生和 NF-κB 活性抑制。
酮康唑、克霉唑、卢立康唑、特比萘芬、布替萘芬和阿莫罗芬等抗真菌药物可能通过增加角质形成细胞中 15d-PGJ2 的产生来抑制 NF-κB，从而抑制 poly I:C 加 IL-4 诱导的 TSLP 产生。这些抗真菌药物可能阻断特应性皮炎皮损中 TSLP 的过度表达。
