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5-氨基酮戊酸光动力疗法通过 MAPK 通路抑制 IFN-γ诱导的 HaCaT 细胞中 K17 的表达。

Photodynamic therapy with 5-aminolevulinic acid suppresses IFN-γ-induced K17 expression in HaCaT cells via MAPK pathway.

机构信息

Department of Dermatology, Qilu Hospital, Shandong University, Jinan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Oct;21(20):4694-4702.

Abstract

OBJECTIVE

Psoriasis is a chronic inflammatory skin disorder that greatly affects the patient's quality of life. Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has recently been applied for inflammatory dermatoses including psoriasis. However, the therapeutic effect of ALA-PDT is yet to be validated, and the underlying mechanisms remain unclear.

MATERIALS AND METHODS

In this study, a psoriatic model was established by treating HaCaT cells with 250 U/ml IFN-γ for 48 h. The effect of ALA-PDT treatment on HaCaT cell viability was assessed using MTT assay. The levels of p38, JNK, and ERK, as well as their phosphorylation status (P-p38, P-JNK, P-ERK), were assessed by immunoblotting.

RESULTS

Our data indicate that ALA-PDT can significantly inhibit the proliferation of IFN-g-treated HaCaT cells and the expression of keratin 17, both in a dose- and time-dependent manner. Furthermore, ALA-PDT can activate the MAPK pathway, and promote the expression of p38, JNK, and ERK. ALA-PDT showed pro-apoptotic effects by enhancing cell apoptosis and upregulating the apoptotic genes PARP and caspase 3.

CONCLUSIONS

Taken together, these findings indicate the possible pathways involved in ALA-PDT-mediated effects and highlight the potential of ALA-PDT in the development of novel therapeutic strategies.

摘要

目的

银屑病是一种慢性炎症性皮肤病,极大地影响了患者的生活质量。5-氨基酮戊酸(ALA)的光动力疗法(PDT)最近已被应用于包括银屑病在内的炎症性皮肤病。然而,ALA-PDT 的治疗效果尚待验证,其潜在机制尚不清楚。

材料和方法

本研究通过用 250 U/ml IFN-γ处理 HaCaT 细胞 48 h 来建立银屑病模型。用 MTT 法评估 ALA-PDT 处理对 HaCaT 细胞活力的影响。用免疫印迹法评估 p38、JNK 和 ERK 及其磷酸化状态(P-p38、P-JNK、P-ERK)的水平。

结果

我们的数据表明,ALA-PDT 可以显著抑制 IFN-γ处理的 HaCaT 细胞的增殖和角蛋白 17 的表达,呈剂量和时间依赖性。此外,ALA-PDT 可以激活 MAPK 通路,并促进 p38、JNK 和 ERK 的表达。ALA-PDT 通过增强细胞凋亡和上调凋亡基因 PARP 和 caspase 3 发挥促凋亡作用。

结论

综上所述,这些发现表明了 ALA-PDT 介导的作用可能涉及的途径,并强调了 ALA-PDT 在开发新的治疗策略方面的潜力。

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