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
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 1044-1549Full text not available from this repository.
Official URL: http://dx.doi.org/10.1165/rcmb.2003-0295OC
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|
|Number of Pages:||9|
|Page Range:||pp. 555-563|
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