The antiglucocorticoid RU486 downregulates the expression of interleukin-2 receptors in normal human lymphocytes

Antonakis, N.; Markogiannakis, E.; Theodoropoulou, M.; Georgoulias, V.; Stournaras, C.; Gravanis, A.

Journal of Steroid Biochemistry and Molecular Biology 39(6): 929-935

1991


ISSN/ISBN: 0960-0760
PMID: 1751392
DOI: 10.1016/0960-0760(91)90351-5
Document Number: 318041
The effects of RU-486, which has anti-glucocorticoid properties, on expression of the interleukin-2 receptors (IL-2R) in human lymphocytes were examined in terms of its dose effect on 2 types of binding sites, and its suppression of beta-chain IL-2R messenger RNA production. Human peripheral lymphocytes stimulated with phytohemagglutinin (PHA) were incubated with the synthetic glucocorticoid dexamethasone and with RU-486 at various doses. Synthesis of 2 types of IL-2R was measured by immunofluorescence assay of the alpha chain. RU-486 inhibits in a dose- dependent fashion the expression of both classes of IL-2R, acting like an agonist. Maximal suppression was seen at a concentration of 10 mcM for the low affinity binding site, and at 1 mcM for the high affinity rate. Messenger RNA was determined by extracting RNA, fractioning it by electrophoresis on agarose gel, and hybridizing with cDNA probes inserted with a plasmid. RU-486 significantly lowered the accumulation of beta-chain IL-2R mRNA transcripts. Thus RU-486 at pharmacological concentrations acts like a glucocorticoid agonist with immunosuppressive effects.

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