Pro-inflammatory mediators induce sustained release of prostaglandin E2 from human dermal microvascular endothelial...

The vasodilator prostaglandin E2 has been proposed as a mediator of erythema in a variety of cutaneous inflammatory reactions and prostacyclin levels have been found to be elevated in ultraviolet induced erythema. Human recombinant interleukin 1 alpha and lipopolysaccharide induced a concentration- and time-dependent release of prostaglandin E2, but not prostacyclin, from cultured neonatal and adult human dermal microvascular endothelial cells. Prostaglandin E2 was measurable at 2 h after stimulation with 1 U/ml interleukin 1 alpha, levels increased rapidly up to 6 h and more slowly up to 24 h. Lipopolysaccharide (20 micrograms/ml) induced measurable release of prostaglandin E2 between 2 and 4 h after stimulation and release continued up to 24 h when incubation was terminated. With both agonists, release of prostaglandin E2 was inhibited by indomethacin and significantly reduced by cycloheximide. The sensitivity and magnitude of responses of the cutaneous endothelial cells to these pro-inflammatory stimuli appeared to be dependent on their derivation.