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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

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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, PGF2a 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-1βstimulated 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-1βon 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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Authors and Affiliations

  1. Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland School of Medicine, Private Bag, 92019, Auckland, New Zealand

    Jeffrey A. Keelan PhD, Timothy A. Sato MSc, Deepak K. Gupta PhD, Keith W. Marvin PhD & Murray D. Mitchell DSc

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  1. Jeffrey A. Keelan PhD
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  2. Timothy A. Sato MSc
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  3. Deepak K. Gupta PhD
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  4. Keith W. Marvin PhD
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  5. Murray D. Mitchell DSc
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Corresponding author

Correspondence to Jeffrey A. Keelan PhD.

Additional information

This study was funded by grants from the Health Research Council of New Zealand, the New Zealand Lottery Health Grants Board, and the Auckland Medical Research Foundation.

The authors thank the nursing staff at National Women’s Hospital, Auckland, for help in assisting with the collection of tissues; Dr. N. Onai, Department of Preventative Medicine, University of Tokyo, for the interleukin (IL)-8 cDNA; and Dr. T. Fukuda, Osaka University Medical School, for the gift of the IL-6 cDNA.

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Keelan, J.A., Sato, T.A., Gupta, D.K. et al. Prostanoid Stimulation of Cytokine Production in an Amnion-Derived Cell Line: Evidence of a Feed-Forward Mechanism With Implications for Term and Preterm Labor. Reprod. Sci. 7, 37–44 (2000). https://doi.org/10.1177/107155760000700106

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