The Effects of Mucopolysaccharide Polysulfate on Steroid-Induced Tight Junction Barrier Dysfunction in Human Epidermal Keratinocytes and a 3D Skin Model.

IF 2.8 4区医学 Q2 DERMATOLOGY Skin Pharmacology and Physiology Pub Date : 2023-01-01 Epub Date: 2023-03-25 DOI:10.1159/000529962

Akira Koda, Yuko Ishii, Ayu Kashiwagi, Mika Fujikawa, Keisuke Kikuchi, Ryota Hashimoto, Yuhki Ueda, Takaaki Doi

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Abstract

Introduction: The long-term use of topical corticosteroids (TCS) is associated with side effects such as skin atrophy and barrier deterioration. Moisturizers, such as mucopolysaccharide polysulfate (MPS), have been reported to prevent relapses in atopic dermatitis (AD) when used in combination with TCS. However, the mechanisms underlying the positive effects of MPS in combination with TCS in AD are poorly understood. In the present study, we investigated the effects of MPS in combination with clobetasol 17-propionate (CP) on tight junction (TJ) barrier function in human epidermal keratinocytes (HEKa) and 3D skin models.

Methods: The expression of claudin-1, which is crucial for TJ barrier function in keratinocytes, and transepithelial electrical resistance (TEER) was measured in CP-treated human keratinocytes incubated with and without MPS. A TJ permeability assay, using Sulfo-NHS-Biotin as a tracer, was also conducted in a 3D skin model.

Results: CP reduced claudin-1 expression and TEER in human keratinocytes, whereas MPS inhibited these CP-induced effects. Moreover, MPS inhibited the increase in CP-induced TJ permeability in a 3D skin model.

Conclusion: The present study demonstrated that MPS improved TJ barrier impairment induced by CP. The improvement of TJ barrier function may partially be responsible for the delayed relapse of AD induced by the combination of MPS and TCS.

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粘多糖聚硫酸盐对类固醇诱导的人表皮角质形成细胞紧密连接屏障功能障碍的影响及三维皮肤模型。

长期使用外用皮质类固醇(TCS)与皮肤萎缩和屏障恶化等副作用有关。保湿剂，如粘多糖聚硫酸盐(MPS)，有报道称与TCS联合使用可预防特应性皮炎(AD)复发。然而，MPS联合TCS治疗AD的积极作用机制尚不清楚。在本研究中，我们研究了MPS联合氯倍他索17-丙酸(CP)对人表皮角质形成细胞(HEKa)和3D皮肤模型紧密连接(TJ)屏障功能的影响。方法:测定经cp处理的人角质形成细胞中对TJ屏障功能至关重要的cludin -1的表达和经上皮电阻(TEER)。使用磺胺- nhs -生物素作为示踪剂，还在3D皮肤模型中进行了TJ通透性测定。结果:CP降低人角质形成细胞中cludin -1的表达和TEER，而MPS则抑制CP诱导的这些作用。此外，在3D皮肤模型中，MPS抑制了cp诱导的TJ通透性的增加。结论:本研究表明，MPS可改善CP所致的TJ屏障功能损害，TJ屏障功能的改善可能是MPS与TCS联用延迟AD复发的部分原因。

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来源期刊

Skin Pharmacology and Physiology 医学-皮肤病学

CiteScore

5.20

自引率

7.40%

发文量

审稿时长

>12 weeks

期刊介绍： In the past decade research into skin pharmacology has rapidly developed with new and promising drugs and therapeutic concepts being introduced regularly. Recently, the use of nanoparticles for drug delivery in dermatology and cosmetology has become a topic of intensive research, yielding remarkable and in part surprising results. Another topic of current research is the use of tissue tolerable plasma in wound treatment. Stimulating not only wound healing processes but also the penetration of topically applied substances into the skin, this novel technique is expected to deliver very interesting results.

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