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

Jeffrey A. Keelan, PhD

Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland, j.kelan{at}auckland.ac.nz

Timothy A. Sato, MSc

Deepak K. Gupta, PhD

Keith W. Marvin, PhD

Murray D. Mitchell, DSc

Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Auckland, New Zeland

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, PGF2{alpha} 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-1ß-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-1ß 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.

Key Words: Amnion • thromboxane • interleukin-6 • interleukin-8 • preterm labor

Journal of the Society for Gynecologic Investigation, Vol. 7, No. 1, 37-44 (2000)
DOI: 10.1177/107155760000700106
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