Corticosteroids suppress cyclooxygenase messenger RNA levels and prostanoid synthesis in cultured vascular cells.
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.
Bailey
J M
JM
Biochemistry Department, George Washington University School of Medicine, Washington, D.C. 20037.
Makheja
A N
AN
Pash
J
J
Verma
M
M
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
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