膳食花青素飞燕草素在银屑病全层三维重组人皮肤模型中的促分化、抗炎和抗增殖作用
Prodifferentiation, anti-inflammatory and antiproliferative effects of delphinidin, a dietary anthocyanidin, in a full-thickness three-dimensional reconstituted human skin model of psoriasis.
作者信息
Chamcheu Jean Christopher, Pal Harish C, Siddiqui Imtiaz A, Adhami Vaqar M, Ayehunie Seyoum, Boylan Brendan T, Noubissi Felicite K, Khan Naghma, Syed Deeba N, Elmets Craig A, Wood Gary S, Afaq Farrukh, Mukhtar Hasan
机构信息
Department of Dermatology, University of Wisconsin-Madison, Madison, Wisc., USA.
出版信息
Skin Pharmacol Physiol. 2015;28(4):177-88. doi: 10.1159/000368445. Epub 2015 Jan 22.
BACKGROUND
Psoriasis is a chronic inflammatory disorder of skin and joints for which conventional treatments that are effective in clearing the moderate-to-severe disease are limited due to long-term safety issues. This necessitates exploring the usefulness of botanical agents for treating psoriasis. We previously showed that delphinidin, a diet-derived anthocyanidin endowed with antioxidant and anti-inflammatory properties, induces normal epidermal keratinocyte differentiation and suggested its possible usefulness for the treatment of psoriasis [1].
OBJECTIVES
To investigate the effect of delphinidin (0-20 μM; 2-5 days) on psoriatic epidermal keratinocyte differentiation, proliferation and inflammation using a three-dimensional reconstructed human psoriatic skin equivalent (PSE) model.
METHODS
PSEs and normal skin equivalents (NSEs) established on fibroblast-contracted collagen gels with respective psoriatic and normal keratinocytes and treated with/without delphinidin were analyzed for histology, expression of markers of differentiation, proliferation and inflammation using histomorphometry, immunoblotting, immunochemistry, qPCR and cultured supernatants for cytokine with a Multi-Analyte ELISArray Kit.
RESULTS
Our data show that treatment of PSE with delphinidin induced (1) cornification without affecting apoptosis and (2) the mRNA and protein expression of markers of differentiation (caspase-14, filaggrin, loricrin, involucrin). It also decreased the expression of markers of proliferation (Ki67 and proliferating cell nuclear antigen) and inflammation (inducible nitric oxide synthase and antimicrobial peptides S100A7-psoriasin and S100A15-koebnerisin, which are often induced in psoriatic skin). ELISArray showed increased release of psoriasis-associated keratinocyte-derived proinflammatory cytokines in supernatants of the PSE cultures, and this increase was significantly suppressed by delphinidin.
CONCLUSIONS
These observations provide a rationale for developing delphinidin for the management of psoriasis.
背景
银屑病是一种皮肤和关节的慢性炎症性疾病，由于长期安全性问题，有效清除中重度疾病的传统治疗方法有限。这就需要探索植物制剂治疗银屑病的有效性。我们之前表明，飞燕草素是一种具有抗氧化和抗炎特性的饮食来源花青素，可诱导正常表皮角质形成细胞分化，并提示其可能对银屑病治疗有用[1]。
目的
使用三维重建的人银屑病皮肤等效物（PSE）模型，研究飞燕草素（0 - 20 μM；2 - 5天）对银屑病表皮角质形成细胞分化、增殖和炎症的影响。
方法
在成纤维细胞收缩的胶原凝胶上建立的PSE和正常皮肤等效物（NSE），分别用银屑病和正常角质形成细胞处理，并在有/无飞燕草素的情况下进行处理，使用组织形态计量学、免疫印迹、免疫化学、qPCR分析组织学、分化、增殖和炎症标志物的表达，并使用多分析物ELISA阵列试剂盒分析培养上清液中的细胞因子。
结果
我们的数据表明，用飞燕草素处理PSE可诱导（1）角质化而不影响细胞凋亡，（2）分化标志物（半胱天冬酶 - 14、丝聚蛋白、兜甲蛋白、内披蛋白）的mRNA和蛋白质表达。它还降低了增殖标志物（Ki67和增殖细胞核抗原）和炎症标志物（诱导型一氧化氮合酶以及抗菌肽S100A7 - 银屑素和S100A15 - 柯布纳素，这些在银屑病皮肤中常被诱导）的表达。ELISA阵列显示PSE培养上清液中银屑病相关角质形成细胞衍生的促炎细胞因子释放增加，而这种增加被飞燕草素显著抑制。
结论
这些观察结果为开发飞燕草素用于银屑病管理提供了理论依据。
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