Mechanism of cytokine stimulation of prostaglandin biosynthesis in human decidua.
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. 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. 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. 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.