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-2R alpha) 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-2R alpha in T cells. Thus, in the present study, we investigated whether IL-1 affects the kinetics of IL-6-induced IL-2R alpha expression in M1 cells. By cytofluorometry, we find that surface expression of IL-2R alpha 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-2R alpha. 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-2R alpha surface expression after treatment with IL-6 and IL-1 occurs in parallel with an increase in IL-2R alpha but not IL-2R beta mRNA expression. By nuclear run-on analysis and actinomycin-D chase experiments, we find that the increase in IL-2R alpha mRNA expression is due to both an increase in IL-2R alpha gene transcription and to an increase in IL-2R alpha mRNA stability. These data suggest that the IL-6-induced expression of IL-2R alpha can be specifically up-regulated by IL-1, however, without affecting the transient nature in expression of IL-2R alpha.
Ruhl
S
S
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD 20892.
Schwabe
M
M
Pluznik
D H
DH
D000208:Acute Disease; D000818:Animals; D015152:Blotting, Northern; D001853:Bone Marrow / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D003609:Dactinomycin; D004357:Drug Synergism; D005434:Flow Cytometry; D006207:Half-Life; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007951:Leukemia, Myeloid; D051379:Mice; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D003609:Dactinomycin