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蛇床子素抑制特应性皮炎 3D 皮肤器官模型中与 Toll 样受体 2 信号通路相关基因的表达。

Osthole Inhibits Expression of Genes Associated with Toll-like Receptor 2 Signaling Pathway in an Organotypic 3D Skin Model of Human Epidermis with Atopic Dermatitis.

机构信息

Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland.

Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, 80-211 Gdańsk, Poland.

出版信息

Cells. 2021 Dec 28;11(1):88. doi: 10.3390/cells11010088.

DOI:10.3390/cells11010088
PMID:35011650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8750192/
Abstract

The Toll-like receptor (TLR) family signature has been linked to the etiopathology of atopic dermatitis (AD), a chronic inflammatory skin disease associated with skin barrier dysfunction and immune system imbalance. We aimed to investigate whether osthole (a plant-derived compound) can inhibit the genetic profile of key genes associated with TLR2 signaling (, , , , , ) after stimulation with LPS or histamine in a 3D in vitro model of AD. Overexpression of the aforementioned genes may directly increase the secretion of proinflammatory cytokines (CKs) and chemokines (ChKs), which may exacerbate the symptoms of AD. Relative gene expressions were quantified by qPCR and secretion of CKs and ChKs was evaluated by ELISA assay. LPS and histamine increased the relative expression of genes related to the TLR2 pathway, and osthole successfully reduced it. In summary, our results show that osthole inhibits the expression of genes associated with the TLR signaling pathway in a skin model of AD. Moreover, the secretion of CKs and ChKs after treatment of AD with osthole in a 3D skin model in vitro suggests the potential of osthole as a novel compound for the treatment of AD.

摘要

Toll 样受体 (TLR) 家族特征与特应性皮炎 (AD) 的发病机制有关,AD 是一种慢性炎症性皮肤病,与皮肤屏障功能障碍和免疫系统失衡有关。我们旨在研究在 AD 的体外 3D 模型中,在 LPS 或组氨酸刺激后,蛇床子素(一种植物衍生的化合物)是否可以抑制与 TLR2 信号转导相关的关键基因的遗传特征(、、、、、)。上述基因的过表达可能直接增加促炎细胞因子 (CKs) 和趋化因子 (ChKs) 的分泌,从而加重 AD 的症状。通过 qPCR 定量相对基因表达,通过 ELISA 测定评估 CKs 和 ChKs 的分泌。LPS 和组氨酸增加了与 TLR2 途径相关的基因的相对表达,而蛇床子素成功地降低了它。总之,我们的结果表明,蛇床子素抑制 AD 皮肤模型中与 TLR 信号通路相关的基因表达。此外,在体外 3D 皮肤模型中用蛇床子素治疗 AD 后 CKs 和 ChKs 的分泌表明蛇床子素作为治疗 AD 的新型化合物具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bf9/8750192/1f87b8acf013/cells-11-00088-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bf9/8750192/1f87b8acf013/cells-11-00088-g008.jpg

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