Differential regulation of macrophage CCAAT-enhancer binding protein isoforms by lipopolysaccharide and cytokines

The regulation of the C/EBP family in macrophages by LPS and cytokines is o f potentially crucial importance in several pathophysiological conditions. The action of LPS and three cytokines on the expression of C/EBP mRNA, prot ein and functional DNA binding activity in the murine J774.2 cell line was therefore studied. Exposure of the cells to LPS, IL-1, IFN-gamma and TNF-al pha produced a reduction of C/EBP alpha mRNA levels and a corresponding inc rease in the expression of C/EBP beta and C/EBP delta. EMSA showed time-dep endent changes in the DNA binding activity of individual C/EBP isoforms and demonstrated the participation of heterodimers between the different membe rs in DNA-protein interactions. Additionally, mediator-specific changes in the kinetics and magnitude of C/EBP mRNA expression pattern and profile of DNA-protein interactions were observed, These studies provide novel insight s into the potential mechanisms that may be responsible for the mediator-sp ecific regulation of macrophage gene expression through the C/EBP family. ( C) 2000 Academic Press.