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 expression in the murine macrophage J774.2 cell line was, therefore, studied. Exposure 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 mobility shift assays showed a close correlation between the expression of the AP-1 genes and the functional AP-1 DNA binding activity and, additionally, demonstrated the participation of heterodimeric interactions between the different 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.
Tengku-Muhammad
T S
TS
Cardiff School of Biosciences, Cardiff University, Cardiff, UK.
Hughes
T R
TR
Foka
P
P
Cryer
A
A
Ramji
D P
DP
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D016762:Genes, fos; D016758:Genes, jun; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma