sphingosine-1-phosphate and Skin-Diseases

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.

Topics: Animals; Ceramides; Dermatitis; Lysophospholipids; Mammals; Skin Diseases; Sphingolipids; Sphingosine

The bioactive lysophospholipid sphingosine-1-phosphate (S1P) is best known for its activity as T-cell-active chemoattractant regulating the egress of T cells from the lymph node and, consequently, the availability of T cells for migration into peripheral tissues. This physiological role of S1P is exploited by the drug fingolimod, a first-line therapy for multiple sclerosis, which "detains" T cells in the lymph nodes. In recent year, it has been elucidated that S1P exerts regulatory functions far beyond T-cell egress from the lymph node. Thus, it additionally regulates, among others, homing of several immune cell populations into peripheral tissues under inflammatory conditions. In addition, evidence, mostly derived from mouse models, has accumulated that S1P may be involved in the pathogenesis of several inflammatory skin disorder and that S1P receptor modulators applied topically are effective in treating skin diseases. These recent developments highlight the pharmacological modulation of the S1P/S1P receptor system as a potential new therapeutic strategy for a plethora of inflammatory skin diseases. The impact of S1P receptor modulation on inflammatory skin diseases next requires testing in human patients.

Topics: Animals; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Lymphocytes; Lysophospholipids; Receptors, Lymphocyte Homing; Receptors, Lysophospholipid; Skin Diseases; Sphingosine; Thiazoles

Dendritic cells (DCs) are the cutting edge in innate and adaptive immunity. The major functions of these antigen-presenting cells are the capture, endosomal processing and presentation of antigens, providing them an exclusive ability to provoke adaptive immune responses and to induce and control tolerance. Immature DCs capture and process antigens, migrate towards secondary lymphoid organs where they present antigens to naive T cells in a well-synchronized sequence of procedures referred to as maturation. Indeed, recent research indicated that sphingolipids are modulators of essential steps in DC homeostasis. It has been recognized that sphingolipids not only modulate the development of DC subtypes from precursor cells but also influence functional activities of DCs such as antigen capture, and cytokine profiling. Thus, it is not astonishing that sphingolipids and sphingolipid metabolism play a substantial role in inflammatory diseases that are modulated by DCs. Here we highlight the function of sphingosine 1-phosphate (S1P) on DC homeostasis and the role of S1P and S1P metabolism in inflammatory diseases.

Topics: Adaptive Immunity; Animals; Antigens; Cytokines; Dendritic Cells; Humans; Immunity, Innate; Lysophospholipids; Skin Diseases; Sphingosine; Toll-Like Receptors; Transcriptome

This review summarizes data on the role of lysosphingolipids (glucosyl- and galactosylsphingosines, sphingosine-1-phosphate, sphingosine-1-phosphocholine) in the regulation of various biological processes in normal and pathological states.

Topics: Animals; Apoptosis; Cardiovascular Diseases; Cell Survival; Humans; Lysophospholipids; Psychosine; Skin Diseases; Sphingolipids; Sphingosine

Topics: Humans; Lysophospholipids; Skin; Skin Diseases; Sphingosine; Wound Healing