ABSTRACT
Sphingolipids are the principal constituents of the plasma membrane as well as a source of important signaling molecules such as ceramide, ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P). Advances in our understanding of sphingolipid biology have made it clear that the intracellular mechanism for the generation and activation of sphingolipid-derived mediators is dynamic inside living cells. Distinct cell surface receptors have been identi™ed and characterized that mediate the responses of these lipid mediators. Evidence is emerging that supports the idea that ceramide, C1P, sphingosine, and S1P play important roles in different inŠammatory diseases, including bronchial asthma. In this chapter, we shall look at the evidence supporting a role of sphingolipid mediators in airway inŠammation. We shall also recapitulate sphingolipid metabolism, the proinŠammatory role of sphingolipidderived products, and the receptors that mediate sphingolipid responses. Among the different sphingolipids, S1P receptors have been key targets for drug discovery. On
12.1 Introduction ..................................................................................................285 12.2 Sphingolipid Biosynthesis.............................................................................286 12.3 Biology of Sphingolipids ..............................................................................287 12.4 Sphingolipids and Airway InŠammation ..................................................... 289
12.4.1 Ceramide ........................................................................................... 289 12.4.2 Sphingosine-1-Phosphate and Sphingosine Kinases ........................290
