Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells
- Univ. of Texas Medical School, Houston (United States)
Prostaglandin H (PGH) synthase 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 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-({sup 35}S)methionine incorporation into PGH synthase that was induced by IL0-1 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.
- OSTI ID:
- 5015848
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:6; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ACETYLSALICYLIC ACID
AMINO ACIDS
ANALGESICS
ANIMAL TISSUES
ANTIPYRETICS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DAYS LIVING RADIOISOTOPES
DNA
DRUGS
EICOSANOIC ACID
ENDOTHELIUM
ENZYMES
EVEN-ODD NUCLEI
GROWTH FACTORS
HYDROXY ACIDS
HYDROXYLASES
INHIBITION
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
LYMPHOKINES
METHIONINE
MITOGENS
MONOCARBOXYLIC ACIDS
NUCLEI
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDOREDUCTASES
PHARMACOLOGY
PROSTAGLANDINS
PROTEINS
RADIOISOTOPES
RECOMBINANT DNA
SULFUR 35
SULFUR ISOTOPES
TISSUES