Mechanism of interleukin-1 beta stimulation of human amnion prostaglandin biosynthesis: mediation via a novel inducible cyclooxygenase.
We have evaluated the mechanism by which interleukin-1 beta (IL-1 beta) increases amnion cell PGE2 production in a concentration-dependent manner. IL-1 beta-stimulated amnion cell PGE2 biosynthesis was time-dependent, and significant stimulation occurred within 2 h of incubation. IL-1 beta stimulation occurred in the presence of added arachidonic acid but was abrogated by treatment with cycloheximide and actinomycin D. Amnion cells treated with IL-1 beta recovered rapidly from aspirin pretreatment suggesting an action on fatty acid cyclooxygenase (COX). Increased amounts of COX protein were demonstrated by Western blot analysis within 2 h of IL-1 beta treatment of amnion cells. Northern blot analysis using a probe specific for a novel form of COX (COX-II) showed an increase in mRNA for this COX within 30 min. This finding using a homologous detection system and human cells of fetal origin in primary culture provides strong support for a physiological role for COX-II in man.
Mitchell
M D
MD
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132.
Edwin
S S
SS
Lundin-Schiller
S
S
Silver
R M
RM
Smotkin
D
D
Trautman
M S
MS
D000650:Amnion / Q000187:drug effects* / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; D003609:Dactinomycin; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin