3.1.4.54 | down |
the pro-inflammatory bacterial endotoxin, lipopolysaccharide, decreases palmitoylethanolamide biosynthesis in RAW264.7 macrophages by suppressing the transcription of NAPE-PLD, which catalyzes the production of palmitoylethanolamide and other lipid amides. Liopolysaccharide treatment reduces acetylation of histone proteins bound to the NAPE-PLD promoter, an effect that is blocked by the histone deacetylase inhibitor richostatin A. The transcription factor Sp1 is involved in regulating baseline NAPE-PLD expression, but not in the transcriptional suppression induced by lipopolysaccharide. The down-regulation of NAPE-PLD expression may be functionally important because mutant NAPE-PLD-null mice, in which this regulatory process is defective, are unable to mount a normal inflammatory reaction in response to carrageenan |
710010 |