Restricted accessResearch articleFirst published online 2000-1
Prostanoid Stimulation of Cytokine Production in an Amnion-Derived Cell Line: Evidence of a Feed-Forward Mechanism With Implications for Term and Preterm Labor
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, PGF2α 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.
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