Dexamethasone inhibits IL-1 and TNF activity in human lung fibroblasts without affecting IL-1 or TNF receptors.
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.
Monick
M M
MM
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
Aksamit
T R
TR
Geist
L J
LJ
Hunninghake
G W
GW
D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D003907:Dexamethasone; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012313:RNA; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors