Interleukin-1 stimulates prostacyclin production by cultured human endothelial cells by increasing arachidonic acid mobilization and conversion.
Interleukin-1 (IL-1) induced slow, lasting activation of human endothelial cells (EC) to release prostacyclin (PGI2). This was accompanied by endogenous 3H-arachidonic acid (3H-AA) release and by a time-dependent increase in the cells' ability to convert exogenous AA. The continuous presence of IL-1 was not required, but about a 1-hour stimulation with the cytokine was sufficient to trigger the cells to synthesize PGI2 for several hours. The spectrum of 3H-AA conversion shows that, in addition to 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha also was raised after IL-1. The recovery of PGI2 synthesis after aspirin was faster in IL-1-treated EC than in control cells. These data define some of the characteristics of IL-1 stimulation of PGI2 and suggest that this process is mediated both by endogenous AA mobilization and by an increase in cyclooxygenase activity.
Breviario
F
F
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Proserpio
P
P
Bertocchi
F
F
Lampugnani
M G
MG
Mantovani
A
A
Dejana
E
E
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D001095:Arachidonic Acids; D007375:Interleukin-1; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin