Research Article| Volume 44, ISSUE 4, P241-245, December 1991

Synergistic stimulation of amnion cell prostaglandin E2 synthesis by interleukin-1, tumor necrosis factor and products from activated human granulocytes

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      We examined the interactions between supernatant from FMLP-activated human granulocytes, recombinant interleukin-1 (IL-1) and recombinant tumor necrosis factor (TNF) in the stimulation of prostaglandin E2 (PGE2) production by human amnion cells. Amnion cells from elective term cesarian sections were cultured in monolayer culture. Human granulocytes were activated with FMLP and centrifuged to obtain cell-free supernatant. Amnion cells were treated with granulocyte supernatant, IL-1α, IL-1β, TNF-α, TNF-β, or different combinations of these. Each of the stimulators alone enhanced the PGE2 production 5-to 27-fold. Granulocyte supernatant was synergistic with each of the cytokines. The combinations of IL-1α or IL-1β with either TNF-α or TNF-β caused a synergistic stimulation of amnion cell PGE2 production as well, whereas the combinations of IL-1α with IL-1β or of TNF-β with TNF-β were not synergistic. Furthermore, granulocyte supernatant was synergistic with the combination of IL-1 and TNF, resulting in a more than 150-fold stimulation of PGE2 production. Indomethacin completely suppressed these effects. We propose that granulocyte products acting together with IL-1 and TNF enhance PGE2 synthesis during inflammation, and serve as signals for the initiation of preterm labor in the setting of intra-amniotic infection.
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