Modulation of ceramide metabolism in mouse primary macrophages.
Ceramide kinase (CERK) produces the bioactive lipid ceramide 1-phosphate (C1P) and is, together with glucosylceramide synthase (GCS) and sphingomyelin synthases (SMS-1 and -2), a key regulator of ceramide metabolism. Here, we used a previously validated assay for measuring CERK, GCS, and SMS activities simultaneously, to study the regulation of ceramide metabolism in mouse macrophages. Elicitation of peritoneal macrophages as well as differentiation of bone marrow-derived monocytes into macrophages led to "ceramide anabolic switching" by re-directing ceramide anabolism towards C1P synthesis by CERK. In contrast, macrophage activation by lipopolysaccharide (LPS) evoked a "ceramide anabolic switch" going in the opposite direction, i.e. featuring up-regulation of GCS and SMS and down-regulation of CERK. The LPS effects were partially blocked by dexamethasone, a known macrophage de-activator. Altogether, the data reveal a contrasting regulation of ceramide metabolism enzymes during macrophage biological responses.
Rovina
Philipp
P
Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1235 Vienna, Austria.
Graf
Christine
C
Bornancin
Frédéric
F
D000818:Animals; D002518:Ceramides / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*
D002518:Ceramides; D008070:Lipopolysaccharides; C065576:ceramide 1-phosphate; D003907:Dexamethasone; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase