Mechanisms of regulation of the MacMARCKS gene in macrophages by bacterial lipopolysaccharide

Bacterial lipopolysaccharide (LPS) stably induced the protein kinase C substrate, MacMARCKS, in murine resident peritoneal macrophages; initial induction 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 responses to LPS. In murine bone marrow‐derived macrophages, MacMARCKS was expressed constitutively due to induction by macrophage colony‐stimulating factor. Nuclear run‐on transcription revealed that, like tumor necrosis factor α (TNF‐α), MacMARCKS was transcribed constitutively in RAW264 cells. The MacMARCKS promoter was sequenced to –1.7 kb and the transcription start site determined. Transient transfections of RAW264 cells revealed that 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. J. Leukoc. Biol. 66: 528–534; 1999.