Thakoersing Varsha S, van Smeden Jeroen, Boiten Walter A, Gooris Gert S, Mulder Aat A, Vreeken Rob J, El Ghalbzouri Abdoelwaheb, Bouwstra Joke A
Department of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Department of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Exp Dermatol. 2015 Sep;24(9):669-74. doi: 10.1111/exd.12740. Epub 2015 Jul 14.
Our in-house human skin equivalents contain all stratum corneum (SC) barrier lipid classes, but have a reduced level of free fatty acids (FAs), of which a part is mono-unsaturated. These differences lead to an altered SC lipid organization and thereby a reduced barrier function compared to human skin. In this study, we aimed to improve the SC FA composition and, consequently, the SC lipid organization of the Leiden epidermal model (LEM) by specific medium supplements. The standard FA mixture (consisting of palmitic, linoleic and arachidonic acids) supplemented to the medium was modified, by replacing protonated palmitic acid with deuterated palmitic acid or by the addition of deuterated arachidic acid to the mixture, to determine whether FAs are taken up from the medium and are incorporated into SC of LEM. Furthermore, supplementation of the total FA mixture or that of palmitic acid alone was increased four times to examine whether this improves the SC FA composition and lipid organization of LEM. The results demonstrate that the deuterated FAs are taken up into LEMs and are subsequently elongated and incorporated in their SC. However, a fourfold increase in palmitic acid supplementation does not change the SC FA composition or lipid organization of LEM. Increasing the concentration of the total FA mixture in the medium resulted in a decreased level of very long chain FAs and an increased level of mono-unsaturated FAs, which lead to deteriorated SC lipid properties. These results indicate that SC lipid properties can be modulated by specific medium supplements.
我们内部的人体皮肤等效物包含所有角质层（SC）屏障脂质类别，但游离脂肪酸（FAs）水平降低，其中一部分是单不饱和脂肪酸。与人类皮肤相比，这些差异导致SC脂质组织改变，从而屏障功能降低。在本研究中，我们旨在通过特定的培养基补充剂来改善莱顿表皮模型（LEM）的SC FA组成，进而改善其SC脂质组织。通过用氘代棕榈酸替代质子化棕榈酸或向混合物中添加氘代花生酸，对添加到培养基中的标准FA混合物（由棕榈酸、亚油酸和花生四烯酸组成）进行了改良，以确定FAs是否从培养基中摄取并掺入LEM的SC中。此外，将总FA混合物或单独的棕榈酸补充量增加四倍，以检查这是否能改善LEM的SC FA组成和脂质组织。结果表明，氘代FAs被摄取到LEMs中，随后被延长并掺入其SC中。然而，棕榈酸补充量增加四倍并不会改变LEM的SC FA组成或脂质组织。增加培养基中总FA混合物的浓度会导致超长链FAs水平降低和单不饱和FAs水平升高，这会导致SC脂质特性变差。这些结果表明，SC脂质特性可以通过特定的培养基补充剂进行调节。
