IL-7 enhances the expression of IL-3 and granulocyte-macrophage-CSF mRNA in activated human T cells by post-transcriptional mechanisms.

Abstract

The stromal derived growth factor IL-7 was studied for its ability to modulate cytokine expression in human T cells. IL-7 alone did not induce IL-3 or granulocyte-macrophage-CSF (GM-CSF) mRNA. However, IL-7 enhanced the Con A-induced IL-3 and GM-CSF mRNA accumulation in a dose-dependent way. mRNA stability studies revealed that the effect of IL-7 was caused by post-transcriptional stabilization of the IL-3 and GM-CSF transcripts. Upon Con A treatment, the IL-3 and GM-CSF mRNA decayed with a t1/2 of approximately 90 and 50 min, respectively. Costimulation with Con A plus IL-7 stabilized both transcripts to t1/2 of greater than 2 h for IL-3 mRNA and 90 min for GM-CSF mRNA. Using nuclear run-on assays, we showed that the transcription rate of both genes was not affected by IL-7. Furthermore, it appeared that the effect of IL-7 was independent on protein synthesis, because cycloheximide did not abolish the promotive effect of IL-7. Finally, it was shown that in accordance with the mRNA results IL-7 enhanced the secretion of GM-CSF protein in Con A-activated T cells. After 12 h of stimulation T cells cultured in the presence of Con A secreted 575 +/- 309 pg GM-CSF/ml (x +/- SD, n = 5), which increased to 1425 +/- 758 pg/ml in the presence of Con A plus IL-7 (p < 0.01). In summary, these data demonstrate that IL-7 augments the expression and secretion of CSF in activated human T cells.

Characterization of the RNA binding proteins forming complexes with a novel putative regulatory region in the 3'-UTR of TNF-alpha mRNA

“…A second destabilizing element beside the ARE in its 3′-UTR was also identified in the coding region of c-myc (39) and in the 5′-UTR of β-interferon (42). The increase in GM-CSF mRNA levels in T lymphocytes induced by various stimuli is not attributable to enhanced levels of transcription, but rather to a significant increase in mRNA stability (43,44). Iwai and colleagues (45) demonstrated that the stabilizing effect of TPA on mRNA containing the GM-CSF 3′-UTR requires both the AU-rich sequence and an additional region located 100-160 nt upstream of the AU-rich element.…”