AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 1 33-L38, Copyright © 1994 by American Physiological Society
Dexamethasone inhibits IL-1 and TNF activity in human lung fibroblasts without affecting IL-1 or TNF receptors
M. M. Monick, T. R. Aksamit, L. J. Geist and G. W. Hunninghake
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
Interleukin (IL-1) and tumor necrosis factor (TNF) activate human lung
fibroblasts through interactions with specific receptors. One effect of
this interaction of IL-1 and TNF with fibroblasts is an increased
production of the cytokines, IL-6 and IL-8. Dexamethasone blocks the
induction of IL-6 and IL-8 by IL-1 or TNF. In these studies, we determined
whether dexamethasone interferes with the upregulation of IL-6 and IL-8 by
downregulating expression of the IL-1 or TNF receptor genes. Confluent lung
fibroblasts were treated with medium alone (control) or medium with
dexamethasone (10(-6) M). Dexamethasone did not decrease the binding of
IL-1 and TNF to their receptors, nor did it decrease amounts of IL-1 or TNF
receptor RNA. Both IL-1 and TNF increased release of IL-6 and IL-8 from the
cells in a dose-dependent manner and dexamethasone inhibited this effect.
Dexamethasone also inhibited the induction of IL-6 and IL-8 RNA by IL-1 and
TNF. The studies show that dexamethasone does not block the effects of IL-1
or TNF on fibroblasts by decreasing expression of IL-1 or TNF receptors.
