Regulation of cell migration and inflammation by ceramide 1-phosphate

Ceramide 1-phosphate (C1P) is a bioactive sphingolipid metabolite first shown to regulate cell growth and death. Subsequent studies revealed that C1P was a potent stimulator of cytosolic phospholipase A2 (cPLA(2)) with ensuing release of arachidonic acid and prostaglandin biosynthesis. The latter findings placed C1P on the list of pro-inflammatory metabolites. More recently, C1P was found to potently stimulate cell migration, an action that is associated to diverse physiological effects, as well as to inflammatory responses and tumor dissemination. The implication of C1P in inflammation has gained further interest in the last few years due to the discovery that it can exert anti-inflammatory actions in some cell types and tissues. In particular, C1P has been demonstrated to inhibit pro-inflammatory cytokine release and blockade of the pro-inflammatory transcription factor NF-kappa B in some cell types, as well as to reduce airway inflammation and lung emphysema. The present review is focused on novel aspects of C1P regulation of cell migration and the impact of C1P as novel anti-inflammatory agent. Gloss: Ceramide 1-phosphate (C1P) is a phosphosphingolipid with potent biological activities. It promotes cell growth and survival, and is a key regulator of cell migration. Both C1P and the enzyme that catalyzes its biosynthesis, ceramide kinase, are implicated in inflammatory responses. Although C1P has pro-inflammatory properties, it reduces pulmonary emphysema and exerts anti-inflammatory actions in the lung. Synthetic C1P analogs may be promising tools to treat lung inflammation. (C) 2016 Elsevier B.V. All rights reserved.