Cytokine-mediated differential regulation of macrophage activator protein-1 genes

The regulation of macrophage activator protein-1 (AP-1) gene expression by LPS and cytokines is of potentially crucial importance in the pathogenesis of several diseases. The action of LPS and four cytokines on AP-1 gene expr ession in the murine macrophage J774.2 cell line was, therefore, studied, E xposure of the cells to IL-6 produced no changes in the mRNA levels of all AP-1 members studied. In contrast, the expression of JunB, c-jun and c-fos, but not JunD, was increased by LPS, TNF-alpha, IFN-gamma and IL-1, albeit with different kinetics and magnitude of induction. Electrophoretic mobilit y shift assays showed a close correlation between the expression of the AP- 1 genes and the functional AP-1 DNA binding activity and, additionally, dem onstrated the participation of heterodimeric interactions between the diffe rent members. These studies provide insights into the potential mechanisms that may be involved in the mediator-specific modulation of AP-1 regulated macrophage gene expression. (C) 2000 Academic Press.