Transcriptional repression of ceramide kinase in LPS-challenged macrophages.
Ceramide kinase (CERK) produces the bioactive lipid ceramide 1-phosphate (C1P). Both CERK and C1P have been identified as mediators of cell growth and survival. Recent evidence showed that CERK is down-regulated during M1-type macrophage activation, which is known to promote cell growth arrest. However, the mechanism has not been investigated yet and, in particular, whether growth arrest might be the signal for down-regulation of CERK is currently unknown. Here, we found that LPS-mediated TLR-4 engagement reduces Cerk mRNA levels in mouse primary macrophages. Reporter gene assays in RAW264.7 macrophages showed that LPS inhibits the transcriptional activity of the Cerk proximal promoter. The G1-cell cycle blocker mimosine did not inhibit Cerk transcription, suggesting that transcriptional repression of Cerk by LPS is not a primary consequence of LPS-induced cell cycle blockade.
Rovina
Philipp
P
Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1235 Vienna, Austria.
Jaritz
Markus
M
Bornancin
Frédéric
F
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D014158:Transcription, Genetic
D008070:Lipopolysaccharides; D017853:Phosphotransferases (Alcohol Group Acceptor); C066324:ceramide kinase