INTERLEUKIN-1 AUGMENTS THE EXPRESSION OF THE INTERLEUKIN-2 RECEPTOR ALPHA-CHAIN IN INTERLEUKIN-6-STIMULATED MYELOID CELLS BY A TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISM

We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2Ralpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2Ralpha in T cells. Thus, in the present study, we investigated whether IL-1 affects the kinetics of IL-6-induced IL-2Ralpha expression in M1 cells. By cytofluorometry, we find that surface expression of IL-2Ralpha at 24 h after induction by IL-6 is strongly enhanced by IL-1. However, IL-1 does not change the transient kinetics of expression of IL-2Ralpha. Binding data and Scatchard analysis support these results and show an increase from 3100 to 17,620 low-affinity IL-2 binding sites per cell without any change in affinity after induction of M1 cells by the combination of IL-6 and IL-1. By Northern analysis, we find that the increase in IL-2Ralpha surface expression after treatment with IL-6 and IL-1 occurs in parallel with an increase in IL-2Ralpha but not IL-2Rbeta mRNA expression. By nuclear run-on analysis and actinomycin-D chase experiments, we find that the increase in IL-2Ralpha mRNA expression is due to both an increase in IL-2Ralpha gene transcription and to an increase in IL-2Ralpha mRNA stability. These data suggest that the IL-6-induced expression of IL-2Ralpha can be specifically up-regulated by IL-1, however, without affecting the transient nature in expression of IL-2Ralpha.