Kleuser Burkhard, Japtok Lukasz
Department of Toxicology, University of Potsdam, Nuthetal, Potsdam, Germany.
Handb Exp Pharmacol. 2013(216):355-72. doi: 10.1007/978-3-7091-1511-4_18.
Mammalian skin protects our body against external assaults due to a well-organized skin barrier. The formation of the skin barrier is a complex process, in which basal keratinocytes lose their mitotic activity and differentiate to corneocytes. These corneocytes are embedded in intercellular lipid lamellae composed of ceramides, cholesterol, fatty acids, and cholesterol esters. Ceramides are the dominant lipid molecules and their reduction is connected with a transepidermal water loss and an epidermal barrier dysfunction resulting in inflammatory skin diseases. Moreover, bioactive sphingolipid metabolites like ceramide-1-phosphate, sphingosylphosphorylcholine, and sphingosine-1-phosphate are also involved in the biological modulation of keratinocytes and immune cells of the skin. Therefore, it is not astonishing that a dysregulation of sphingolipid metabolism has been identified in inflammatory skin diseases such as atopic dermatitis and psoriasis vulgaris. This chapter will describe not only the specific sphingolipid species and their skin functions but also the dysregulation of sphingolipid metabolism in inflammatory skin diseases.
哺乳动物的皮肤凭借组织良好的皮肤屏障保护我们的身体免受外部侵害。皮肤屏障的形成是一个复杂的过程,在此过程中,基底角质形成细胞失去其有丝分裂活性并分化为角质形成细胞。这些角质形成细胞嵌入由神经酰胺、胆固醇、脂肪酸和胆固醇酯组成的细胞间脂质层中。神经酰胺是主要的脂质分子,其减少与经表皮水分流失和表皮屏障功能障碍相关,进而导致炎症性皮肤病。此外,生物活性鞘脂代谢物,如神经酰胺 -1- 磷酸、鞘氨醇磷酸胆碱和鞘氨醇 -1- 磷酸,也参与皮肤角质形成细胞和免疫细胞的生物调节。因此,在特应性皮炎和寻常型银屑病等炎症性皮肤病中发现鞘脂代谢失调也就不足为奇了。本章不仅将描述特定的鞘脂种类及其皮肤功能,还将阐述炎症性皮肤病中鞘脂代谢的失调情况。