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特应性皮炎和银屑病患者表皮中的初级纤毛增多。

Increase in primary cilia in the epidermis of patients with atopic dermatitis and psoriasis.

机构信息

Laboratory of Advanced Cosmetic Science, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.

Laboratory of Mock up Vaccine, Center for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.

出版信息

Exp Dermatol. 2021 Jun;30(6):792-803. doi: 10.1111/exd.14285. Epub 2021 Feb 12.

Abstract

Primary cilia influence cell activity, and thus have a unique role in maintaining cell proliferation and differentiation. In atopic dermatitis (AD) and psoriasis, areas of skin inflammation exhibit dysregulated keratinocyte homeostasis. The role of primary cilia in these conditions remains unclear. The objectives of this study is to elucidate the incidence of primary cilia in skin inflammation and the potential mechanism underlying the dysregulation of keratinocytes. Primary cilia were observed using immunofluorescence staining. Normal skin samples were compared with skin samples from patients with AD or psoriasis in terms of cilia numbers and length. The effect of cytokine stimulation on ciliogenesis in keratinocytes was analysed using a primary keratinocyte culture. IFT88, an important ciliary intraflagellar protein, was blocked in Th2 and Th17 cytokines-stimulated keratinocytes. These effects were analysed with quantitative polymerase chain reaction and Western blot. Significant increases in ciliated cells were observed in AD and psoriasis skin samples compared with normal skin samples. The stimulation of keratinocytes using Th2 and Th17 cytokines modulated the formation of primary cilia. The amount of IFT88 in the primary cilia associated with the phosphorylation of JNK, but not p38, in keratinocytes stimulated with interleukin-13, 17A and 22. An increase of ciliated cells in the epidermis may impair keratinocyte differentiation under stress conditions caused by inflammation in both AD and psoriasis patients.

摘要

原发性纤毛影响细胞活性,因此在维持细胞增殖和分化方面具有独特的作用。在特应性皮炎(AD)和银屑病中,皮肤炎症区域表现出角质形成细胞稳态失调。原发性纤毛在这些情况下的作用尚不清楚。本研究旨在阐明皮肤炎症中原发性纤毛的发生率以及角质形成细胞失调的潜在机制。使用免疫荧光染色观察原发性纤毛。比较正常皮肤样本和 AD 或银屑病患者的皮肤样本中的纤毛数量和长度。使用原代角质形成细胞培养物分析细胞因子刺激对角质形成细胞纤毛发生的影响。IFT88,一种重要的纤毛内鞭毛蛋白,在 Th2 和 Th17 细胞因子刺激的角质形成细胞中被阻断。用定量聚合酶链反应和 Western blot 分析这些影响。与正常皮肤样本相比,AD 和银屑病皮肤样本中观察到有丝分裂细胞的数量显著增加。Th2 和 Th17 细胞因子刺激角质形成细胞,调节初级纤毛的形成。与 p38 不同,在白细胞介素-13、17A 和 22 刺激的角质形成细胞中,与 JNK 磷酸化相关的初级纤毛中的 IFT88 数量增加。表皮中有丝分裂细胞的增加可能会损害 AD 和银屑病患者炎症引起的应激条件下的角质形成细胞分化。

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