Mechanism of interleukin-1β stimulation of human amnion prostaglandin biosynthesis: Mediation via a novel inducible cyclooxygenase

We have evaluated the mechanism by which interleukin-1β (IL-1β) increases amnion cell PGE₂ production in a concentration-dependent manner. IL-1β-stimulated amnion cell PGE₂ biosynthesis was time-dependent, and significant stimulation occurred within 2 h of incubation. IL-1β stimulation occurred in the presence of added arachidonic acid but was abrogated by treatment with cycloheximide and actinomycin D. Amnion cells treated with IL-1β 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-1β 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.