Interleukin-4 inhibits interleukin-1 alpha-induced granulocyte- macrophage
colony-stimulating factor gene expression in a murine B- lymphocyte cell
line via downregulation of RNA precursor
K Akahane and DH Pluznik
Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD
20892.
Interleukin-4 (IL-4) regulates the growth of B cells. When combined with
colony-stimulating factors (CSFs) and selected cytokines, IL-4 has a
synergistic effect on the clonal growth of bone marrow cells. Recently, we
have shown that IL-1 alpha and lipopolysaccharide induce expression of the
granulocyte-macrophage CSF (GM-CSF) gene in murine B- cell lines. In the
present study, we show that IL-4 inhibits the production of GM-CSF in the
IL-1 alpha-stimulated murine B-cell line M12.4.1. IL-4 did not change the
transcription rate of the GM-CSF gene, and caused only a slight decrease in
cytoplasmic GM-CSF messenger RNA (mRNA) half-life in cells treated with
IL-1 alpha. PCR analysis of nuclear RNA with probes specific for GM-CSF
intron sequences suggests that IL-1 alpha enhances accumulation of nuclear
precursor RNA and that decreased GM-CSF expression after IL-4 treatment is
mainly due to intranuclear destabilization of the primary transcript. Under
the same experimental conditions, IL-4 did not affect expression of the
IL-4 receptor mRNA and did increase the mRNA concentration of the low-
affinity receptor for IgE (Fc epsilon RII). These data suggest that the
suppressive effect of IL-4 is specific for GM-CSF mRNA expression, and thus
provide evidence for an additional role of IL-4 in the regulation of GM-CSF
expression in B cells.
Volume 79,
Issue 12,
pp. 3188-3195,
06/15/1992
Copyright © 1992 by The American Society of Hematology
