Interferon-gamma antagonizes interleukin-6-induced expression of interleukin-4 receptors in murine myeloid cells by a transcriptional mechanism

Blood. 1993 Nov 1;82(9):2641-8.

Abstract

The murine myeloid leukemia cell line M1 induced by interleukin-6 (IL-6) is a model system to study the differentiation of blast cells to mature macrophages. We have recently shown that IL-6 induces the expression of the IL-4 receptor (IL-4R) in these cells. In the present study we investigate the mechanism of action of interferon-gamma (IFN-gamma), an antagonist of IL-4 in numerous cells and a cofactor in both induction and suppression of myelopoiesis, on the expression of IL-4R. Flow cytometry shows that IFN-gamma downregulates the IL-6-induced expression of IL-4R whereas it has no such effect on the high-affinity receptors for monomeric IgG2a (Fc gamma RI). As demonstrated by Scatchard analysis, the number of IL-4R decreases by more than 50% after IFN-gamma treatment whereas the receptor affinity remains unchanged. Northern analysis shows that this decrease is paralleled by a decrease in IL-4R mRNA but not Fc gamma RI or lysozyme mRNA. Nuclear run-on analysis shows that IFN-gamma suppresses the IL-6-induced transcription of the IL-4R gene, whereas actinomycin-D chase experiments showed no change of IL-4R mRNA stability. Furthermore, the production of soluble IL-4R protein is suppressed by IFN-gamma as well. These data explain how IL-4R can be modulated by IFN-gamma in myeloid cells and are consistent with the myelosuppressive capacity of IFN-gamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Interferon-gamma / pharmacology*
  • Interleukin-6 / antagonists & inhibitors*
  • Leukemia, Myeloid / metabolism*
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Mice
  • Muramidase / genetics
  • RNA, Messenger / analysis
  • Receptors, IgG / analysis
  • Receptors, Interleukin-4
  • Receptors, Mitogen / analysis
  • Receptors, Mitogen / biosynthesis*
  • Receptors, Mitogen / genetics
  • Transcription, Genetic / drug effects*
  • Tumor Cells, Cultured

Substances

  • Interleukin-6
  • RNA, Messenger
  • Receptors, IgG
  • Receptors, Interleukin-4
  • Receptors, Mitogen
  • Interferon-gamma
  • Muramidase