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Regulatory Effect on Skin Differentiation by Mevastatin in Psoriasis Model Using TNF-α and IL-17 Induced HaCaT Cells
Biotechnology and Bioprocess Engineering ( IF 2.5 ) Pub Date : 2021-07-12 , DOI: 10.1007/s12257-020-0368-z
Min Young Kim 1 , Hyung Seo Hwang 1 , You Won Choi 2
Affiliation  

Mevastatin (HMG-CoA reductase inhibitor) isolated from Penicillium citrinum is known to the first statin that inhibitor of cholesterol synthesis. Recently, several clinical reports of other statins suggest its role on reducing the severity of psoriasis, but the available evidence on cellular/molecular level of mevastatin is unclear. Thus, this study was to determine the molecular/cellular mechanism of mevastatin using TNF-α/IL-17A stimulated HaCaT cells. First, the safety and effectiveness of mevastatin were confirmed through the comparative experiment of five statin derivatives. Mevastatin decreased mRNA levels of cytokines (IL-1α/β, IL-6, and IL-8), chemokine (CC motif) ligand 20 (CCL20), and keratin proteins (Keratin 5/14/6/16) known to be overexpressed in psoriasis. In addition, mevastatin significantly reduced phosphorylation of NF-κB, MAPKs and STAT3 in TNF-α/IL-17 signaling pathway. Moreover, mevastatin specifically suppressed keratin 5/14 proteins expressed in the keratinocyte differentiation process of the basal layer and keratin 6A/16 overexpressed in patients with psoriasis. These results imply that mevastatin not only can inhibit psoriasis-induced inflammatory cytokines and chemokines, but also can suppress psoriasis-related keratin proteins.



中文翻译:

在使用 TNF-α 和 IL-17 诱导的 HaCaT 细胞的银屑病模型中,美伐他汀对皮肤分化的调节作用

柑橘青霉中分离出的美伐他汀(HMG-CoA 还原酶抑制剂)是已知的第一个他汀类药物,即胆固醇合成抑制剂。最近,其他他汀类药物的一些临床报告表明其在降低银屑病严重程度方面的作用,但关于美伐他汀细胞/分子水平的现有证据尚不清楚。因此,本研究旨在使用 TNF-α/IL-17A 刺激的 HaCaT 细胞确定美伐他汀的分子/细胞机制。首先,通过五种他汀类药物衍生物的对比实验,证实了美伐他汀的安全性和有效性。美伐他汀降低细胞因子(IL-1α/β、IL-6 和 IL-8)、趋化因子(CC 基序)配体 20(CCL20)和角蛋白(角蛋白 5/14/6/16)的 mRNA 水平。在银屑病中过度表达。此外,美伐他汀显着降低了 TNF-α/IL-17 信号通路中 NF-κB、MAPK 和 STAT3 的磷酸化。而且,美伐他汀特异性抑制基底层角质形成细胞分化过程中表达的角蛋白 5/14 蛋白和银屑病患者中过表达的角蛋白 6A/16。这些结果意味着美伐他汀不仅可以抑制银屑病诱导的炎性细胞因子和趋化因子,还可以抑制银屑病相关的角蛋白。

更新日期:2021-07-12
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