Sphingosine 1-Phosphate as Essential Signaling Molecule in Inflammatory Skin Diseases

Abstract

Sphingolipids are crucial molecules of the mammalian epidermis. The formation of skin-specific ceramides contributes to the formation of lipid lamellae, which are important for the protection of the epidermis from excessive water loss and protect the skin from the invasion of pathogens and the penetration of xenobiotics. In addition to being structural constituents of the epidermal layer, sphingolipids are also key signaling molecules that participate in the regulation of epidermal cells and the immune cells of the skin. While the importance of ceramides with regard to the proliferation and differentiation of skin cells has been known for a long time, it has emerged in recent years that the sphingolipid sphingosine 1-phosphate (S1P) is also involved in processes such as the proliferation and differentiation of keratinocytes. In addition, the immunomodulatory role of this sphingolipid species is becoming increasingly apparent. This is significant as S1P mediates a variety of its actions via G-protein coupled receptors. It is, therefore, not surprising that dysregulation in the signaling pathways of S1P is involved in the pathophysiological conditions of skin diseases. In the present review, the importance of S1P in skin cells, as well as the immune cells of the skin, is elaborated. In particular, the role of the molecule in inflammatory skin diseases will be discussed. This is important because interfering with S1P signaling pathways may represent an innovative option for the treatment of inflammatory skin diseases.

Efficacy and Safety of S1P1 Receptor Modulator Drugs for Patients with Moderate-to-Severe Ulcerative Colitis

“…S1P plays a fundamental role in the immune system. It has been evaluated as a therapeutic target for several immune-mediated disorders beyond UC, such as multiple sclerosis (MS) [64,65], psoriasis [66], rheumatoid arthritis [67], systemic lupus erythematosus [68]. In fact, ozanimod has been authorized for clinically isolated syndrome, relapsing-remitting MS by the EMA and for active secondary progressive MS by the FDA [27].…”

Serum lipidomics‐based study of electroacupuncture for skin wound repair in rats

“…In the sphingomyelinase pathway, CER is formed by hydrolysis of sphingomyelins in the granular layer of the skin by sphingomyelinase. CERs are considered to be one of the most important epidermal sphingolipids, accounting for approximately 50% of the intercellular lipids of the SC 35,36 The CERs are transported from the endoplasmic reticulum to the Golgi apparatus, where the conversion to glucosyl CERs or sphingomyelin occurs 37 . Signalling pathways such as protein kinase B (Akt), protein kinase C (PKC), mitogen‐activated protein kinase (MAPK), Jun amino‐terminal kinase (JNK), or phospholipase D (PLD) are regulated during CER stimulation 38 .…”

“…CERs are considered to be one of the most important epidermal sphingolipids, accounting for approximately 50% of the intercellular lipids of the SC 35 , 36 The CERs are transported from the endoplasmic reticulum to the Golgi apparatus, where the conversion to glucosyl CERs or sphingomyelin occurs. 37 Signalling pathways such as protein kinase B (Akt), protein kinase C (PKC), mitogen‐activated protein kinase (MAPK), Jun amino‐terminal kinase (JNK), or phospholipase D (PLD) are regulated during CER stimulation. 38 Although the importance of CER in skin cell proliferation and differentiation has long been known, in recent years sphingosine 1‐phosphate sphingosine (S1P) has also been found to be involved in processes such as the proliferation and differentiation of keratin‐forming cells.…”

The role of sphingosine-1-phosphate in autophagy and related disorders

“…The degradation of intracellular S1P occurs in the ER: dephosphorylation into sphingosine through S1P phosphatases (SPPs) or irreversible cleavage into ethanolamine phosphate by S1P lyase (SGPL1) [ 17 ]. Extracellular S1P is mainly degraded via lipid phosphate phosphatases (LPPs) at the cell plasma membrane [ 18 ].

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