全身性 ALA-PDT 能有效阻止银屑病样损伤的发展，并减轻 K14-VEGF 转基因小鼠中的白细胞浸润。

Systemic ALA-PDT effectively blocks the development of psoriasis-like lesions and alleviates leucocyte infiltration in the K14-VEGF transgenic mouse.

机构信息

Department of Dermatovenereology, Chengdu Second People's Hospital, Chengdu, Sichuan, China.

Department of Dermatovenereology, West PR China Hospital of Sichuan University, Chengdu, Sichuan, China.

出版信息

Clin Exp Dermatol. 2017 Dec;42(8):849-856. doi: 10.1111/ced.13148. Epub 2017 Jun 9.

DOI:10.1111/ced.13148

PMID:28597992

Abstract

BACKGROUND

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders. In spite of significant advances in the treatment of psoriasis, more effective and safer therapeutic strategies are still needed. Photodynamic therapy (PDT) is a method of light treatment that is being used increasingly in the treatment of dermatological diseases.

AIM

To evaluate the therapeutic effects of systemic 5-aminolaevulinic acid (ALA)-PDT on psoriasis and to explore its potential mechanism of action.

METHODS

We investigated the therapeutic effects of systemic ALA-PDT in K14-vascular endothelial growth factor (VEGF) transgenic homozygous mice, an animal model of psoriasis, which has many clinical and histopathological characteristics similar to those of human psoriasis. Using haematoxylin and eosin staining, immunohistochemistry and real-time quantitative PCR respectively, we assessed the changes in psoriasis-like lesions, cellular infiltration of T cells, dendritic cells (DCs) and neutrophils, and the mRNA expression of the inflammatory cytokines interleukin (IL)-17 and interferon (IFN)-γ in the lesions.

RESULTS

Systemic ALA-PDT blocked the development of psoriasis-like lesions and moderately attenuated the histopathological changes in K14-VEGF transgenic mice. Furthermore, systemic ALA-PDT produced an obvious reduction in infiltration of T cells, CD11c+ DCs and neutrophils in psoriasis-like lesions. In addition, systemic ALA-PDT also significantly decreased the mRNA expression of IL-17 and IFN-γ.

CONCLUSIONS

We suggest that the mechanism of systemic ALA-PDT in this psoriasis-like model might be associated with selective damage to abnormal T helper (Th)1 and Th17 cells, and reduction of the inflammatory cytokines IL-17 and IFN-γ. These observations partly explain the potential mechanism of systemic ALA-PDT in psoriasis and other inflammatory skin diseases.

摘要

背景

银屑病是最常见的免疫介导的慢性炎症性皮肤疾病之一。尽管在银屑病的治疗方面取得了重大进展，但仍需要更有效和更安全的治疗策略。光动力疗法（PDT）是一种光疗方法，越来越多地用于治疗皮肤病。

目的

评估全身性 5-氨基酮戊酸（ALA）-PDT 治疗银屑病的疗效，并探讨其潜在的作用机制。

方法

我们研究了全身性 ALA-PDT 在 K14-血管内皮生长因子（VEGF）转基因纯合子小鼠中的治疗效果，该动物模型具有许多与人类银屑病相似的临床和组织病理学特征。我们分别使用苏木精和伊红染色、免疫组织化学和实时定量 PCR 评估银屑病样病变、T 细胞、树突状细胞（DC）和中性粒细胞的细胞浸润以及病变中炎症细胞因子白细胞介素（IL）-17 和干扰素（IFN）-γ 的 mRNA 表达的变化。

结果

全身性 ALA-PDT 阻断了银屑病样病变的发展，并适度减轻了 K14-VEGF 转基因小鼠的组织病理学变化。此外，全身性 ALA-PDT 导致银屑病样病变中 T 细胞、CD11c+DC 和中性粒细胞的浸润明显减少。此外，全身性 ALA-PDT 还显著降低了 IL-17 和 IFN-γ 的 mRNA 表达。