Hanke J H, Nichols L N, Coon M E
Molecular Genetics Research Department, Pfizer, Inc., Groton, CT 06340.
Lymphokine Cytokine Res. 1992 Oct;11(5):221-31.
The macrolides FK506 and rapamycin are potent immunosuppressive agents that inhibit the activation of T cells. Using Northern analyses and promoter-reporter constructs we analyzed the transcriptional and posttranscriptional effects of FK506 and rapamycin on IL-2, GM-CSF, and IL-2R alpha gene expression. FK506 completely inhibited activation of the IL-2 promoter, but only partially blocked GM-CSF promoter activity. In contrast, rapamycin only partially inhibited IL-2 and GM-CSF promoter activity. Interestingly, both FK506 and rapamycin also destabilized both IL-2 and GM-CSF mRNAs without influencing the stability of either the IL-2R alpha or GAPDH mRNA. These results show that both FK506 and rapamycin modulate IL-2 and GM-CSF gene expression at both the transcriptional and posttranscriptional level.
