Sphingosine-1-phosphate as signaling molecule in the skin: Relevance in atopic dermatitis

Sphingolipids are essential molecules of the mammalian epidermis. Keratinocytes generate and secrete huge amounts of ceramide-precursors to the extracellular domain of the stratum corneum, where they are further metabolized to specific ceramide species. The arrangement of ceramides to well-organized lipid lamellae is essential to form the epidermal barrier. Besides their role as structural components sphingolipids are also critical molecules involved in the modulation of epidermal cells. Sphingosine-1-phosphate (S1P) has been identified as a prominent signaling molecule which regulates fundamental functions of keratinocytes and skin dendritic cells. Thus, S1P inhibits proliferation of keratinocytes and induces their differentiation. Moreover, antigen uptake, migration and cytokine production of dendritic cells are under the control of this sphingolipid. A dysregulation of the sphingolipid metabolism has been discussed in inflammatory skin disorders like atopic dermatitis. Animal models of contact dermatitis provide evidence that topical treatment with S1P is connected with an anti-inflammatory action suggesting a novel approach for the treatment of atopic dermatitis.