Sphingolipid signaling in epidermal homeostasis - Current knowledge and new therapeutic approaches in dermatology

In the present review we have attempted to give an overview of the role of sphingolipids in skin homoeostasis. Sphingolipid metabolites are emerging a s potent second messengers in diverse cellular signaling pathways. In the s kin little is known about sphingolipids in signaling events. In various cel l populations it has been shown that different sphingolipid metabolites hav e opposing effects on the biological outcome of a stimulus. Therefore, the term 'sphingolipid rheostat' has been established and has also been shown t o exist in skin-derived cell populations. In many cells ceramide is a media tor of proliferation inhibition and apoptosis, whereas sphingosine-1-phosph ate acts more like a growth factor and reverses ceramide effects. In kerati nocytes extracellular and intracellular ceramides play important roles. Ext racellular ceramides are necessary for the water retention capacity and for maintaining the permeability barrier of the skin. Intracellular ceramides cause differentiation of keratinocytes. Until now less is known about the e ffect of other sphingolipid metabolites in the skin. Copyright (C) 2001 S. Karger AG, Basel.