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Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and
IL-6, but not of M-CSF in human fibroblasts
A Tobler, R Meier, M Seitz, B Dewald, M Baggiolini and MF Fey
Central Hematology Laboratory of the University of Berne, Inselspital,
Switzerland.
Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-
CSF), macrophage-CSF (M-CSF), neutrophil-activating peptide-
1/interleukin-8 (NAP-1/IL-8), and interleukin-6 (IL-6) are pivotal in the
regulation of hematopoiesis and immune responses. In mesenchymal cells,
their expression is induced by tumor necrosis factor alpha (TNF) and other
agents. We now show that, while induction of cytokine expression by TNF in
human lung fibroblasts was parallel, glucocorticoid hormones differentially
affected their production. Dexamethasone (1 mumol/L) concordantly repressed
expression of GM-CSF, NAP-1/IL-8 and IL-6. RNA and protein levels were
reduced to approximately 5%, 20%, and 30% of control cells, respectively,
as determined by Northern blot analyses and immunoassays. A 50% reduction
of RNA levels for all three cytokines occurred in the range of 1 hour. In
contrast, dexamethasone (1 mumol/L) did not decrease M-CSF RNA levels and
protein release. M-CSF RNA and protein levels were maintained even when
dexamethasone (1 mumol/L) was present for the whole duration of a 48-hour
TNF stimulation. Further experiments showed that dexamethasone
downregulates expression of GM-CSF, NAP-1/IL-8, and IL-6 mainly by
decreasing the mRNA stability of these cytokines, and that the
dexamethasone-mediated repression of cytokine expression depends on ongoing
protein and RNA syntheses. Our study suggests that glucocorticoid hormones
repress expression of a set of cytokine genes important in conditions of
stress. However, they seem not to affect M- CSF expression, which is likely
to be more crucial in maintaining long- term functions of myeloid cells.
Volume 79,
Issue 1,
pp. 45-51,
01/01/1992
Copyright © 1992 by The American Society of Hematology
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