Interleukin-1 potentiates histamine-induced release of prostacyclin from human endothelial cells.
1. In human cultured umbilical vein endothelial cells, interleukin-1 potentiated histamine-induced release of prostacyclin in a time- and concentration-dependent manner. 2. In cells incubated with interleukin-1 for 24 h, maximal potentiation was observed when cells were pre-incubated with 0.5 u ml-1 interleukin-1 before stimulation with histamine (1 microM-1 mM). 3. In cells incubated with 0.5 u ml-1 interleukin-1, 20 min pre-incubation was sufficient to induce a statistically significant potentiation of prostacyclin release induced by 1 microM histamine (P less than 0.05). 4. Nifedipine but not cycloheximide, significantly (P less than 0.05) inhibited histamine-induced release of prostacyclin and interleukin-1 potentiation of histamine-induced release of prostacyclin (P less than 0.05). 5. Incubation with 1 u ml-1 interleukin-1 induced a two fold increase in cellular prostaglandin synthetase activity within 30 min. The enzyme activity increased up to 6 h and was maintained up to 24 h. In cells co-incubated with cycloheximide and 1 u ml-1 interleukin 1, prostaglandin synthetase activity at 24 h was the same as that in unstimulated cells. Prostacyclin release was not significantly inhibited in cells co-incubated with cycloheximide and interleukin 1. 6. These results suggest that interleukin-1 potentiates histamine-induced release of prostacyclin by rapid up-regulation of prostaglandin synthetase activity as well as by inducing synthesis of enzyme protein. These mechanisms may act to potentiate/regulate vascular endothelial responses in inflammatory reactions.
Bull
H A
HA
Department of Dermatology and Academic Unit, University College & Middlesex School of Medicine, London.
Dowd
P M
PM
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D006632:Histamine / Q000008:administration & dosage*; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage*; D009543:Nifedipine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D007375:Interleukin-1; D006632:Histamine; D003513:Cycloheximide; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D009543:Nifedipine