Dexamethasone and 1,25-dihydroxyvitamin D3, but not cyclosporine A, inhibit
production of granulocyte-macrophage colony-stimulating factor in human
fibroblasts
A Tobler, HP Marti, C Gimmi, AB Cachelin, S Saurer and MF Fey
Department of Medicine, Inselspital Berne, Switzerland.
Tumor necrosis factor alpha (TNF alpha) stimulates granulocyte- macrophage
colony-stimulating factor (GM-CSF) production in human fibroblasts and
other mesenchymal cells. However, relatively little is known about agents
that downregulate cytokine production in these cells. In the present report
we show that dexamethasone (Dexa), a synthetic glucocorticoid, markedly
reduced GM-CSF production in TNF alpha-stimulated fibroblasts at both the
protein and the RNA levels. CSF activity, GM-CSF protein, and RNA levels,
determined by an in vitro colony-forming assay in normal human bone marrow
cells, by an enzyme immunoassay, and by Northern blotting assay, were
reduced to greater than 90% of control values by Dexa (1 mumol/L).
Similarly, 1,25- dihydroxyvitamin D3 [1,25(OH)2D3], a hormone with possible
physiologic immunoregulatory significance, reduced GM-CSF expression in a
concentration- and time-dependent manner. However, this repression was less
pronounced than that of Dexa, and in part due to a decreased proliferative
activity. In contrast, cyclosporine A (CsA), another immunosuppressive
agent, did not alter GM-CSF expression in TNF alpha- stimulated
fibroblasts. Our in vitro studies suggest that by inhibiting GM-CSF
production in fibroblasts, glucocorticoids and possibly 1,25(OH)2D3, but
not CsA, may attenuate TNF alpha-mediated inflammatory processes and
influence the regulation of hematopoiesis.
Volume 77,
Issue 9,
pp. 1912-1918,
05/01/1991
Copyright © 1991 by The American Society of Hematology
