The antiglucocorticoid RU486 downregulates the expression of interleukin-2 receptors in normal human lymphocytes.
The effects of the antiglucocorticoid RU486 on the expression of low and high affinity interleukin-2 receptors (IL-2R) in phytohaemagglutinin (PHA)-activated human peripheral blood lymphocytes were investigated. We demonstrated that RU486 inhibits in a dose-dependent way the expression of both classes of IL-2R, thereby mimicking the effects of the glucocorticoid agonist dexamethasone. The maximal effect on the low affinity binding sites was observed at 10 microM (28 +/- 2% of control, P less than 0.001) and on the high affinity IL-2R at 1 microM (from 2938 +/- 74 to 437 +/- 108 binding sites per cell, P less than 0.001). This inhibition of IL-2R expression occurs at a pretranslational level since RU486 decreased the accumulation of beta-chain IL-2R mRNA transcripts. Our data support the concept that the antiglucocorticoid RU486 at pharmacological concentrations can exert agonistic-immunosuppressive effects.
Antonakis
N
N
Department of Basic Sciences, School of Medicine, University of Crete, Iraklion, Greece.
Markogiannakis
E
E
Theodoropoulou
M
M
Georgoulias
V
V
Stournaras
C
C
Gravanis
A
A
D015152:Blotting, Northern; D015536:Down-Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D015735:Mifepristone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000187:drug effects*; D013936:Thymidine / Q000378:metabolism
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015735:Mifepristone; D013936:Thymidine