Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells.
Prostaglandin H (PGH) synthase (EC 1.14.99.1) is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations (0.1-1 micrograms/ml) inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-[35S]methionine incorporation into PGH synthase that was induced by IL-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate.
Wu
K K
KK
Department of Medicine, University of Texas Medical School, Houston 77030.
Sanduja
R
R
Tsai
A L
AL
Ferhanoglu
B
B
Loose-Mitchell
D S
DS
D000082:Acetaminophen / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D011464:Epoprostenol / Q000096:biosynthesis; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000235:genetics*
D007375:Interleukin-1; D012333:RNA, Messenger; D000082:Acetaminophen; D008715:Methionine; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D007213:Indomethacin