Interferon-gamma antagonizes interleukin-6-induced expression of
interleukin-4 receptors in murine myeloid cells by a transcriptional
mechanism
S Ruhl, GM Feldman, K Akahane and DH Pluznik
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD
20892.
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.
Volume 82,
Issue 9,
pp. 2641-2648,
11/01/1993
Copyright © 1993 by The American Society of Hematology
