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

• Published in: Journal of leukocyte biology Vol. 66; no. 3; pp. 528 - 534
• Main Authors: Chang, Sandy, Stacey, Katryn J., Chen, Jianmin, Costelloe, Elaine O., Aderem, Alan, Hume, David A.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.09.1999
• Subjects: Animals; Base Sequence; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; endotoxin; Gene Expression Regulation - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Intracellular Signaling Peptides and Proteins; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Mice; Molecular Sequence Data; Neoplasm Proteins - biosynthesis; Organ Specificity; Promoter Regions, Genetic; Protein Kinase C - metabolism; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; RNA, Messenger - biosynthesis; RNA, Neoplasm - biosynthesis; Sp1; transcription; Transcription, Genetic - drug effects; Transfection; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.66.3.528

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.