Mechanisms of regulation of the MacMARCKS gene in macrophages by bacteriallipopolysaccharide

Bacterial lipopolysaccharide (LPS) stably induced the protein kinase C subs trate, MacMARCKS, in murine resident peritoneal macrophages; initial induct ion of MacMARCKS mRNA was detected within 15 min and was protein synthesis- independent. This response was observed in the macrophage cell line RAW264, and occurred also in response to plasmid DNA, a partial mimetic of other r esponses to LPS. In murine bone marrow-derived macrophages, MacMARCKS was e xpressed constitutively due to induction by macrophage colony-stimulating f actor. Nuclear run-on transcription revealed that, like tumor necrosis fact or alpha (TNF-alpha), MacMARCKS was transcribed constitutively in RAW264 ce lls. The MacMARCKS promoter was sequenced to -1.7 kb and the transcription start site determined, Transient transfections of RAW264 cells revealed tha t the 113-bp GC-rich proximal promoter contained all the elements required for both high basal activity and 15- to 20-fold activation by LPS.