Mechanism of cytokine stimulation of prostaglandin biosynthesis in human decidua.
OBJECTIVE
The purpose of this study was to determine the mechanism of action of the cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on the stimulation of prostaglandin (PG) production in human decidua.


METHODS
Decidual cells from term placentas were grown in culture until confluent. Incubations were performed with TNF alpha or IL-1 beta, and with cycloheximide, actinomycin D, arachidonic acid, or acetylsalicylic acid (ASA). Prostaglandin E2 was measured by radioimmunoassay and cellular protein determined.


RESULTS
The concentration-related stimulation of decidual PGE2 production by IL-1 beta and TNF alpha was completely abrogated by cycloheximide and actinomycin D treatment. Although arachidonic acid alone stimulated decidual PGE2 biosynthesis, the addition of IL-1 beta or TNF alpha consistently augmented this effect. Both cytokines induced recovery of PGE2 biosynthesis from ASA pretreatment more rapidly than controls.


CONCLUSIONS
Interleukin-1 beta and TNF alpha both act on decidual PG biosynthesis in a manner requiring new protein synthesis. In combination with our other results, this suggests that IL-1 beta and TNF alpha act to induce PG endoperoxide synthase activity.
Pollard
J K
JK
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Thai
D
D
Mitchell
M D
MD
D003513:Cycloheximide / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011453:Prostaglandins; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide