Masuda-Kuroki Kana, Di Nardo Anna
Department of Dermatology, School of Medicine, University of California, San Diego, CA 92093, USA.
Biology (Basel). 2022 May 25;11(6):809. doi: 10.3390/biology11060809.
Sphingosine 1-phosphate (S1P) is a product of membrane sphingolipid metabolism. S1P is secreted and acts via G-protein-coupled receptors, S1PR1-5, and is involved in diverse cellular functions, including cell proliferation, immune suppression, and cardiovascular functions. Recent studies have shown that the effects of S1P signaling are extended further by coupling the different S1P receptors and their respective downstream signaling pathways. Our group has recently reported that S1P inhibits cell proliferation and induces differentiation in human keratinocytes. There is a growing understanding of the connection between S1P signaling, skin barrier function, and skin diseases. For example, the activation of S1PR1 and S1PR2 during bacterial invasion regulates the synthesis of inflammatory cytokines in human keratinocytes. Moreover, S1P-S1PR2 signaling is involved in the production of inflammatory cytokines and can be triggered by epidermal mechanical stress and bacterial invasion. This review highlights how S1P affects human keratinocyte proliferation, differentiation, immunoreaction, and mast cell immune response, in addition to its effects on the skin barrier interface. Finally, studies targeting S1P-S1PR signaling involved in inflammatory skin diseases are also presented.
1-磷酸鞘氨醇（S1P）是膜鞘脂代谢的产物。S1P被分泌出来并通过G蛋白偶联受体S1PR1 - 5发挥作用，参与多种细胞功能，包括细胞增殖、免疫抑制和心血管功能。最近的研究表明，通过耦合不同的S1P受体及其各自的下游信号通路，S1P信号的作用得到了进一步扩展。我们小组最近报道，S1P抑制人角质形成细胞的增殖并诱导其分化。人们对S1P信号、皮肤屏障功能和皮肤疾病之间的联系的认识正在不断加深。例如，在细菌入侵期间S1PR1和S1PR2的激活调节人角质形成细胞中炎性细胞因子的合成。此外，S1P - S1PR2信号传导参与炎性细胞因子的产生，并且可由表皮机械应激和细菌入侵触发。这篇综述重点介绍了S1P如何影响人角质形成细胞的增殖、分化、免疫反应和肥大细胞免疫反应，以及它对皮肤屏障界面的影响。最后，还介绍了针对炎性皮肤病中涉及的S1P - S1PR信号传导的研究。
