title: Corticosteroids suppress cyclooxygenase messenger RNA levels and prostanoid synthesis in cultured vascular cells.
abstract: Prostacyclin synthesis by cultured vascular smooth muscle cells was inactivated by aspirin. Recovery required serum factors replaceable by EGF plus TGF-beta and was blocked by cycloheximide but not by actinomycin D. Recovery of cyclooxygenase activity was prevented by preincubation with dexamethasone (0.1 to 2 microM), which also suppressed basal enzyme activity by up to 70%. A full length 2.8 Kb cDNA hybridization probe for human cyclooxygenase identified a cyclooxygenase messenger RNA of approximately 2.8 Kb in these cells. Cyclooxygenase mRNA levels were enhanced by EGF/TGF-beta, but suppressed completely by corticosteroids. It is concluded that inhibition of prostanoid synthesis by corticosteroids is mediated by suppressing cyclooxygenase messenger RNA. These observations provide a new molecular mechanism for the anti-inflammatory activity of the corticosteroids.
authors.affiliation: Biochemistry Department, George Washington University School of Medicine, Washington, D.C. 20037.
authors.forename: J M
authors.initials: JM
authors.lastname: Bailey
authors.forename: A N
authors.initials: AN
authors.lastname: Makheja
authors.forename: J
authors.initials: J
authors.lastname: Pash
authors.forename: M
authors.initials: M
authors.lastname: Verma
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D003348:Cortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015342:DNA Probes; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015291:Transforming Growth Factors / Q000494:pharmacology
chemical_list: D000305:Adrenal Cortex Hormones; D001095:Arachidonic Acids; D015342:DNA Probes; D011453:Prostaglandins; D012333:RNA, Messenger; D003609:Dactinomycin; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D003907:Dexamethasone; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D003348:Cortisone