Nuclear factor-kappaB does not mediate the inhibitory effects of dexamethasone on granulocyte-macrophage colony-stimulating factor expression

Bergmann, Martin W., Staples, Karl J., Barnes, Peter J. and Newton, Robert (2004) Nuclear factor-kappaB does not mediate the inhibitory effects of dexamethasone on granulocyte-macrophage colony-stimulating factor expression. Immunology, 111 (4), 430-434. (doi:10.1111/j.0019-2805.2004.01833.x).

Abstract

Human granulocyte–macrophage colony-stimulating factor (GM-CSF) reporter constructs containing up to 3·3 kb of upstream promoter sequence were transiently transfected into both Jurkat and HUT78 human T-cell lines. In Jurkat cells, stimulation with phorbol 12-myristate 13-acetate (PMA) plus phytohemaglutinin (PHA) produced robust increases in reporter activity, whereas HUT78 cells showed low levels of reporter induction attributable to constitutive nuclear factor (NF)-?B activity. Following mutation of either the proximal NF-?B site (?85/?76) or the activator protein1 (AP-1) motif within the conserved lymphokine element 0 (CLE0) site (?54/?31), reporter activity was markedly reduced in both cell lines. Despite this dependence on NF-?B and CLE0/AP-1, GM-CSF reporter activity was unaffected by dexamethasone in either cell line. Similarly, an NF-?B-dependent reporter was also not repressed by dexamethasone, yet GM-CSF release from HUT78 T cells was inhibited. These data therefore confirm a critical role for both NF-?B and CLE0 sites in GM-CSF promoter activation and indicate that NF-?B may not mediate glucocorticoid-dependent repression of GM-CSF in these cells

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Contributors

Author: Karl J. Staples

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