STIM/ orai介导的钙进入引起特应性皮炎小鼠表皮细胞自发的TSLP过量产生

M. Fujii, Shuhei Kobayashi, Ayane Ueda, Misaki Sakagami, R. Matsui, Yumeka Yamada, T. Nabe, S. Ohya
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引用次数: 0

摘要

目的:特应性皮炎(AD)是一种瘙痒性慢性炎症性皮肤病。胸腺基质淋巴生成素(TSLP)在AD患者的表皮中高表达,并诱导T辅助2 (Th2)免疫反应和瘙痒。虽然在正常角质形成细胞中刺激诱导的TSLP产生的机制已经被深入研究,但在AD条件下表皮细胞中TSLP的产生能力是否会自然增强尚不清楚。先前的研究表明,缺乏多不饱和脂肪酸(PUFA)会导致特殊饮食喂养的无毛小鼠出现ad样瘙痒性皮肤炎症。本研究旨在探讨饮食诱导的AD小鼠表皮细胞产生TSLP的能力及其机制。方法:分别从正常小鼠和AD小鼠中分离表皮细胞,在无刺激培养条件下观察TSLP的自发生成。采用实时聚合酶链反应(PCR)和酶联免疫吸附试验(ELISA)分别检测TSLP信使核糖核酸(mRNA)和蛋白水平。结果:AD小鼠皮肤中TSLP水平明显升高。分离AD小鼠表皮细胞,无刺激培养时,Tslp基因表达上调,大量Tslp蛋白在细胞外释放。在正常小鼠的表皮细胞中没有观察到这种TSLP的过量产生。胞外钙螯合、干扰质膜间质相互作用分子1 (STIM1)、阻断钙释放活化钙(CRAC)通道Orai1和Orai2,或PUFA γ-亚麻酸(GLA)处理,几乎完全抑制AD表皮细胞中TSLP的过量产生。结论:AD小鼠表皮细胞可通过STIM/ orai介导的钙进入自发产生TSLP, GLA可能负向调节TSLP的产生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
STIM/Orai-mediated calcium entry elicits spontaneous TSLP overproduction in epidermal cells of atopic dermatitis mice
Aim: Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease. Thymic stromal lymphopoietin (TSLP) is highly expressed in the epidermis of patients with AD and induces T helper 2 (Th2) immune responses and itching. Although the mechanism underlying the stimulus-induced TSLP production in normal keratinocytes has been intensively studied, whether the production capability of TSLP is naturally enhanced in epidermal cells in AD conditions remains unclear. Previous studies demonstrated that a deficiency of polyunsaturated fatty acid (PUFA) causes AD-like pruritic skin inflammation in special diet-fed hairless mice. The aim of the study was to examine the TSLP production capability of epidermal cells isolated from diet-induced AD mouse model and its mechanism. Methods: Epidermal cells were isolated from normal and AD mice and incubated under unstimulated culture conditions to assess spontaneous TSLP production. Messenger ribonucleic acid (mRNA) and protein levels of TSLP were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: TSLP level was markedly increased in the skin of AD mice. When epidermal cells were isolated from AD mice and cultured without stimulation, Tslp gene expression was upregulated, and a large amount of TSLP protein was extracellularly released. Such TSLP overproduction was not observed in the epidermal cells of normal mice. TSLP overproduction in AD epidermal cells was almost completely inhibited by extracellular calcium chelation, interference with plasma membrane interaction of stromal interaction molecule 1 (STIM1), blockade of the calcium release-activated calcium (CRAC) channels Orai1 and Orai2, or treatment with a PUFA γ-linolenic acid (GLA). Conclusions: Epidermal cells isolated from AD mice can spontaneously produce TSLP through STIM/Orai-mediated calcium entry, and GLA may negatively regulate this TSLP production.
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