RT Journal Article
SR Electronic
T1 Prostaglandin E2 and other cyclic AMP-elevating agents modulate IL-2 and IL-2R alpha gene expression at multiple levels.
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 2845
OP 2852
VO 148
IS 9
A1 Anastassiou, E D
A1 Paliogianni, F
A1 Balow, J P
A1 Yamada, H
A1 Boumpas, D T
YR 1992
UL http://www.jimmunol.org/content/148/9/2845.abstract
AB cAMP is an intracellular second messenger that conveys inhibitory signals for T cell activation and clonal proliferation. cAMP also inhibits the production of IL-2 and IL-2R alpha-chain expression. To determine the mechanisms of this inhibition, human peripheral blood T lymphocytes were stimulated with anti-CD3 mAb, PHA, PMA, or ionomycin, alone or in combination. cAMP elevation by PGE2, cholera toxin, or the cell-permeable analogue 8-bromo-cAMP inhibited the tyrosine phosphorylation of a protein of 100 kDa. This inhibition was associated with decreased IL-2 production and IL-2R alpha expression at both the protein product and the mRNA levels. Nuclear run-off assays showed that the inhibitory effect of cAMP on IL-2 and IL-2R alpha gene expression is mediated at the transcriptional level. H-8, an inhibitor of protein kinase A, reversed the inhibitory effect of cAMP on nuclear transcription of the IL-2 gene, suggesting that this is mediated through activation of protein kinase A. Post-transcriptionally, cAMP elevation decreased the t1/2 of IL-2 mRNA by more than 50%. These data indicate that cAMP inhibits cell membrane, cytoplasmic, and nuclear events associated with T cell activation and highlight the complexities of its action of lymphocyte function.