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Regulation of cytokine expression by interferon-alpha in human bone marrow
stromal cells: inhibition of hematopoietic growth factors and induction of
interleukin-1 receptor antagonist
MJ Aman, U Keller, G Derigs, M Mohamadzadeh, C Huber and C Peschel
Third Department of Medicine, Johannes Gutenberg University School of
Medicine, Mainz, Germany.
We investigated the effects of interferon-alpha (IFN-alpha) on the
expression of cytokines by human bone marrow stromal cells. Production of
granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF
(G-CSF), and interleukin-1 beta (IL-1 beta) in stromal cell layers was
induced by incubation with IL-1 alpha, tumor necrosis factor (TNF), or
lipopolysaccharide (LPS). Addition of IFN-alpha to such stimulated cultures
resulted in a strong downregulation of mRNA expression of GM-CSF and IL-1
beta. Similarly, the protein levels of GM- CSF and IL-1 beta were
significantly reduced by IFN-alpha, whereas G- CSF production was only
moderately inhibited. In contrast, IFN-alpha markedly stimulated the
production of IL-1 receptor antagonist (IL-1RA) by stromal cells. The
inhibition of cytokine expression resulted in a reduced hematopoietic
activity of stromal cells, indicated by a reduced proliferation of the
factor dependent cell line MO7e on IFN-alpha- treated stromal cells. In the
presence of cycloheximide (CHX), IFN- alpha failed to inhibit IL-1 mRNA
expression, whereas the regulation of GM-CSF and IL-1RA by IFN-alpha was
not affected. Our results indicate that the myelosuppressive effects of
IFN-alpha, as observed in therapeutic applications or associated with viral
infections, are, in part, indirectly mediated by inhibition of the
paracrine production of hematopoietic growth factors.
Volume 84,
Issue 12,
pp. 4142-4150,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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