Linked Life Data

8900312

Source:http://linkedlifedata.com/resource/pubmed/id/8900312

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1996-12-4
pubmed:abstractText
In T cells stimulated through the T cell receptor (TCR), both cyclosporine (CsA) and glucocorticoids (GC) inhibit the transcription of the IL-2 gene. In these cells costimulation via the CD28 cell surface molecule further increases the transcription of IL-2 and stabilizes its mRNA, resulting in a 20-30 fold induction in IL-2 production. This pathway is relatively resistant to the inhibitory effect of CsA. In this study, we asked whether GC interfere with CD28-mediated costimulatory signals for T cell activation. Primary human T cells or Jurkat T cells were stimulated with anti-CD28 and phorbol myristate acetate (PMA) in the presence of dexamethasone (Dex, 10(-10)-10(-5) M). Dex inhibited both the mRNA for IL-2 and IL-2 production in a dose-dependent fashion (minimum effective dose 10(-9) M). In similar experiments employing anti-CD3 mAb and PMA, a 7-20 fold higher concentration of Dex was required to obtain comparable inhibition. To determine if transcriptional modulation is occurring, Jurkat T cells were transfected with a plasmid containing the IL-2 promoter linked to the chloramphenicol acetyl transferase reporter gene. Following stimulation with ionomycin and PMA, high doses (10(-6) M) of Dex inhibited the activity of the IL-2 promoter (approximately 50% inhibition). However, in the presence of anti-CD28 mAb, this promoter became resistant to Dex (< or = 10% inhibition). These results suggest that GC inhibit accessory pathways for IL-2 production via CD28 by predominantly posttranscriptional mechanisms. Inhibition of the CD28 pathway may be an important mechanism for the T cell directed immunosuppressive effects of low-to-moderate doses of GC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0041-1337
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1113-8
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Glucocorticoids modulate CD28 mediated pathways for interleukin 2 production in human T cells: evidence for posttranscriptional regulation.
pubmed:affiliation
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article