Interleukin 1 augments the expression of the interleukin 2 receptor alpha-chain in interleukin 6-stimulated myeloid cells by a transcriptional and posttranscriptional mechanism

Exp Hematol. 1992 Nov;20(10):1208-15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Blotting, Northern
  • Bone Marrow / chemistry
  • Bone Marrow / metabolism
  • Bone Marrow / ultrastructure*
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • Dactinomycin
  • Drug Synergism
  • Flow Cytometry
  • Half-Life
  • Interleukin-1 / pharmacology*
  • Interleukin-2 / metabolism
  • Interleukin-6 / pharmacology*
  • Iodine Radioisotopes
  • Leukemia, Myeloid
  • Mice
  • Protein Processing, Post-Translational / genetics*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptors, Interleukin-2 / analysis
  • Receptors, Interleukin-2 / genetics*
  • Receptors, Interleukin-2 / metabolism*
  • Time Factors
  • Transcription, Genetic / genetics*
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Interleukin-1
  • Interleukin-2
  • Interleukin-6
  • Iodine Radioisotopes
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Dactinomycin