FK506 and rapamycin selectively enhance degradation of IL-2 and GM-CSF mRNA.
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.
D001483:Base Sequence; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D011090:Polyenes / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors*; D020123:Sirolimus; D013601:T-Lymphocytes / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D007376:Interleukin-2; D011090:Polyenes; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020123:Sirolimus; D016559:Tacrolimus