Effects of glucocorticoids on transcription factor activation in human peripheral blood mononuclear cells

I. M. Adcock*, C. R. Brown, C. M. Gelder, H. Shirasaki, M. J. Peters, P. J. Barnes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

121 Citations (Scopus)

Abstract

Glucocorticoids have an inhibitory effect on inflammatory and immune responses, and this may be through the modulation of transcription factor binding to DNA. The interaction of the transcription factors, activator protein-1 (AP-1), nuclear factor kappa B (NF(κ)B), and cAMP-responsive element binding protein (CREB) with DNA and glucocorticoid receptors (GR) was analyzed in human peripheral blood mononuclear cells by gel mobility shift assays. TNF-α, IL-2β and phorbol myristate acetate (PMA) treatment increased AP-1 and NFκB DNA binding by up to 200% but decreased CREB binding (38%) over a 60-min time course. Dexamethasone produced a rapid and sustained increase in glucocorticoid response element binding and a concomitant 40-50% decrease in AP-1, NF(κ)B, and CREB DNA binding that was blocked by combined dexamethasone and cytokine or PMA treatment. These latter effects were due to increases in the nuclear localization of GR, not to reduced amounts of the other transcription factors. This suggests that in these cells GR within the nucleus interacts with cytokine-stimulated transcription factors by the process of cross coupling. This may be an important molecular site of steroid action.

Original languageEnglish
Pages (from-to)C331-C338
Number of pages8
JournalAmerican Journal of Physiology - Cell Physiology
Volume268
Issue number2
Publication statusPublished - 1995
Externally publishedYes

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