Introduction

Psoriasis cellular hallmarks, such as the imbalance between Th1/Th17 and Th2 cytokines and the dysregulated expression of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase, (iNOS) and indoleamine 2,3-dioxygenase (IDO), are all detectable in mesenchymal stem cells (MSCs) suggesting that psoriasis originates at mesenchymal level. Aim of the study: In this scenario, MSCs may become the new therapeutic target and interest in the effects of traditionally used drugs, such as Apremilast, on MSCs has greatly increased.

Materials and Methods

MSCs from control subjects (C-MSCs) and from psoriatic patients before (PsO MSCs T0) and after in vivo treatment with Apremilast (PsO-MSCs T12) were isolated and characterized; subsequently, the effects of Apremilast on VEGF, iNOS and IDO expression were evaluated by immunocytochemistry (ICC). The expression of VEGF, iNOS and IDO was also detected in skin sections by immunohistochemistry (IHC).

Results

The results indicate that in vivo administration of Apremilast is able to drive the altered profile of PsO-MSCs towards a more physiological pattern. In skin sections, the role of Apremilast is evident in reducing VEGF, iNOS and IDO expression.

Conclusion

Apremilast treatment influences the expression of VEGF, iNOS and IDO not only by keratinocytes but also by MSCs, restoring their intrinsic profile and their natural anti-inflammatory action, and decreasing the auto-inflammatory process that underpins the development of psoriasis.

中文翻译：

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阿普司特的体内给药对银屑病患者间充质干细胞的疗效

介绍

银屑病的细胞特征，例如 Th1/Th17 和 Th2 细胞因子之间的失衡以及血管内皮生长因子 (VEGF)、诱导型一氧化氮合酶 (iNOS) 和吲哚胺 2,3-双加氧酶 (IDO) 的表达失调，都可以检测到在间充质干细胞 (MSCs) 中表明银屑病起源于间充质水平。研究目的：在这种情况下，MSCs 可能成为新的治疗靶点，并且对传统使用的药物（如 Apremilast）对 MSCs 的影响的兴趣大大增加。

材料和方法

分离和表征来自对照受试者 (C-MSC) 和银屑病患者 (PsO MSC T0) 和 Apremilast 体内治疗后 (PsO-MSC T12) 的 MSC；随后，通过免疫细胞化学（ICC）评估了阿普司特对 VEGF、iNOS 和 IDO 表达的影响。通过免疫组织化学（IHC）还检测了皮肤切片中VEGF、iNOS和IDO的表达。

结果

结果表明，阿普司特的体内给药能够将 PsO-MSCs 的改变谱推向更生理的模式。在皮肤切片中，阿普司特在降低 VEGF、iNOS 和 IDO 表达方面的作用很明显。

结论

阿普斯特治疗不仅通过角质形成细胞而且通过 MSC 影响 VEGF、iNOS 和 IDO 的表达，恢复它们的内在特征和它们的天然抗炎作用，并减少支持银屑病发展的自身炎症过程。