Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Centre for Human Drug Research, Leiden, The Netherlands.
J Lipid Res. 2023 Aug;64(8):100400. doi: 10.1016/j.jlr.2023.100400. Epub 2023 Jun 8.
The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier function. The three main subclasses in the SC lipid matrix are ceramides (CER), cholesterol, and free fatty acids. In inflammatory skin diseases, such as atopic dermatitis and psoriasis, the SC lipid composition is modulated compared to the composition in healthy SC. One of the main alterations is the molar ratio between the concentration of CER N-(tetracosanoyl)-sphingosine (CER NS) and CER N-(tetracosanoyl)-phytosphingosine (CER NP), which correlated with an impaired skin barrier function. In the present study, we investigated the impact of varying the CER NS:CER NP ratios on the lipid organization, lipid arrangement, and barrier functionality in SC lipid model systems. The results indicate that a higher CER NS:CER NP ratio as observed in diseased skin did not alter the lipid organization or lipid arrangement in the long periodicity phase encountered in SC. The trans-epidermal water loss, an indication of the barrier functionality, was significantly higher for the CER NS:CER NP 2:1 model (mimicking the ratio in inflammatory skin diseases) compared to the CER NS:CER NP 1:2 ratio (in healthy skin). These findings provide a more detailed insight into the lipid organization in both healthy and diseased skin and suggest that in vivo the molar ratio between CER NS:CER NP contributes to barrier impairment as well but might not be the main factor.
皮肤最上层的脂质,即角质层(SC),在皮肤屏障功能中起着重要作用。SC 脂质基质的三个主要亚类是神经酰胺(CER)、胆固醇和游离脂肪酸。在炎症性皮肤病,如特应性皮炎和银屑病中,与健康 SC 相比,SC 脂质组成发生了改变。主要的改变之一是 CER N-(二十四烷酰)-神经酰胺(CER NS)和 CER N-(二十四烷酰)-植物神经酰胺(CER NP)浓度的摩尔比,这与皮肤屏障功能受损有关。在本研究中,我们研究了改变 CER NS:CER NP 比例对 SC 脂质模型系统中脂质组织、脂质排列和屏障功能的影响。结果表明,与健康皮肤相比,在疾病皮肤中观察到的更高的 CER NS:CER NP 比例并没有改变在 SC 中遇到的长周期性阶段的脂质组织或脂质排列。作为屏障功能的指示,经表皮水分流失(TEWL)对于 CER NS:CER NP 2:1 模型(模拟炎症性皮肤病中的比例)明显高于 CER NS:CER NP 1:2 比例(在健康皮肤中)。这些发现提供了对健康和患病皮肤中脂质组织的更详细的了解,并表明在体内,CER NS:CER NP 的摩尔比也会导致屏障受损,但可能不是主要因素。