The riddle of the sphinx redux

Abstract

Understanding the mechanisms of glucocorticoid-mediated inhibition of inflammation has been challenging. This is particularly true with regard to the development of drugs that mimic the anti-inflammatory benefits of steroids while avoiding the untoward metabolic effects. Förster et al. report that the inhibition of stress-induced mesangial-cell apoptosis by dexamethasone is mediated by sphingosine-1-phosphate. These findings identify alternative pathways whereby the anti-inflammatory mechanisms of glucocorticoids can be probed.

Figure 1. Simple anabolic pathways governing sphingolipid formation and major bioactive sphingolipids

Bulleted items are examples of associations between major sphingolipids and inflammatory conditions that characterize classic clinical disorders. These disorders include Gaucher’s disease (glucosylceramide); Fabry’s disease and hemolytic uremic syndrome (globotriaosylceramide); Niemann–Pick disease (sphingomyelin); Farber’s disease (ceramide); and brown recluse spider bites (ceramide-1-phosphate). CNS, central nervous system.