UNSPECIFIED. (2004) Glucocorticoid inhibition of granulocyte macrophage-colony-stimulating factor from T cells is independent of control by nuclear factor-kappa B and conserved lymphokine element 0. Journal of Molecular Biology, 30 (4). pp. 555-563. ISSN 1044-1549

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Abstract

Release of granulocyte macrophage-colony-stimulating factor (GM-CSF) from T cells is important in the differentiation, maturation, and survival of inflammatory cells. Here the induction of GMCSF expression from T cells was dependent on transcription and translation and was prevented by dexamethasone. In primary human CD3+ T cells, up to 3.3 kb of human GM-CSF promoter was strongly activated by PMA + PHA. Mutations in either the -85/-76 nuclear factor (NF)-kappaB site or the activator protein-1 region in the -54/-31 conserved lymphokine element 0 (CLEO) site substantially reduced promoter activity. Both GM-CSF promoter and NF-kappaB-dependent constructs were unresponsive to dexamethasone whereas the release of GM-CSF was potently repressed. Analysis of GM-CSF mRNA and protein expression at various time points and the effect of adding dexamethasone after the stimulus revealed the existence of potent mechanisms of inhibition acting at a translational level. The expression of tristetraproline and HuR, proteins that bind the AU-rich element in the GM-CSF 3'-untranslated region was unaffected by dexamethasone and overall AU-rich element binding activity was unaltered. Taken together our data support an important role for the NF-kappaB and CLEO sites in the transcriptional control of GM-CSF expression in primary human T cells and suggest that post-transcriptional/transiational mechanisms are key mediators of glucocorticoid-dependent repression.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine
Journal or Publication Title:	Journal of Molecular Biology
Publisher:	AMER THORACIC SOC
ISSN:	1044-1549
Date:	April 2004
Volume:	30
Number:	4
Number of Pages:	9
Page Range:	pp. 555-563
Identification Number:	10.1165/rcmb.2003-0295OC
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/8566

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