Prostanoid Stimulation of Cytokine Production in an Amnion-Derived Cell Line: Evidence of a Feed-Forward Mechanism With Implications for Term and Preterm Labor

Abstract

Objective: To test the hypothesis that amnion cytokine production might be regulated by prostanoids.

Methods: Amnion-derived WISH cells were treated with a range of prostanoids and their effects on production of interleukin (IL)-6 and IL-8 were determined by enzyme-linked immunosorbent assay and Northern analysis. The effect of thromboxane inhibitors on cytokine production by term primary amnion explants also were examined.

Results: Prostaglandin (PG)A₂, PGD₂, PGF_2α PGE₂, PGJ₂, and the PGI₂ analogue carbaprostacyclin (1-1000 nmol/L) exhibited no significant effects on cytokine production. However, the thromboxane A₂ (TXA₂) agonists U46619 and carbocyclic (c)TXA₂ both stimulated WISH cytokine production with similar potencies under basal or cytokine-stimulated conditions. Significant stimulation of IL-6 production was observed at concentrations ≥8 nmol/L (P < .05 by analysis of variance), whereas IL-8 production was stimulated significantly but to a lesser extent. The effects of U46619 and cTXA₂ were rapid; maximal stimulation of cytokine production occurred within 4 to 8 hours of treatment. U46619 augmented IL-1β-stimulated IL-6 and IL-8 mRNA expression within 2 hours of treatment. In amnion explants inhibitors of TX synthesis and action abrogated the stimulatory effect of IL-1β on cytokine production.

Conclusion: These results are consistent with the presence of a feed-forward loop in amnion involving TXA₂ and cytokines, which could play a significant role in the progression of the inflammatory response involved in the mechanism of infection-driven preterm labor.

Keywords

Amnion thromboxane interleukin-6 interleukin-8 preterm labor

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