Dexamethasone inhibits tumor necrosis factor-induced granulocyte colony-stimulating factor production in human endothelial cells.
Dexamethasone (10(-5)-10(-7) M) is able to suppress the tumor necrosis factor (TNF)-induced production of granulocyte colony-stimulating factor (G-CSF) in human umbilical vein endothelial cells (HUVEC). Using Western-blot analysis and bioassay for the evaluation of G-CSF protein and activity, a significant decrease in TNF-induced production could be found in cells cultured in the presence of dexamethasone as compared to TNF stimulation in the absence of dexamethasone. No inhibition by dexamethasone was seen in endothelial cells stimulated with interleukin 1 beta (IL-1 beta; 10 U/ml). Addition of IL-1 to cultures stimulated with TNF in the presence of dexamethasone could overcome the inhibitory effects of corticosteroids. Suppression of G-CSF production can, at least in part, explain the functional abnormalities of granulocytes found in patients treated with glucocorticosteroids.
Kerner
B
B
Department of Pediatric Hematology and Oncology, Medical School Hannover, Germany.
Teichmann
B
B
Welte
K
K
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D004121:Dimethyl Sulfoxide