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Opposite Effect of Phorbol Ester PMA on PTGS2 and PGDH mRNA Expression in Human Chorion Trophoblast Cells

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Abstract

Prostaglandins (PGs) induce the mechanism of labor in humans. The enzymes responsible for PG synthesis and metabolism are prostaglandin-endoperoxide synthase 2 (PTGS2) and 15-hydroxyprostaglandin dehydrogenase (PGDH). In human chorion trophoblast cells, calcium ionophore A23187 upregulates PTGS2 and downregulates PGDH protein and mRNA. The authors hypothesize that this regulation requires activation of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs). Human chorion trophoblasts were incubated with A23187 or phorbol 12-myristate 13-acetate (PMA) in the absence or presence of inhibitors of PKC, c-Jun N-terminal kinase, p38, and MEK1/2. PTGS2 and PGDH mRNA were measured by real-time reverse-transcription polymerase chain reaction. PMA upregulated PTGS2 and downregulated PGDH. The PMA effect was reversed by the inhibition of PKC. The p38 inhibitor reduced the stimulatory effect of PMA and A23187 on PTGS2. MEK1/2 inhibitor reduced the effect of PMA on PTGS2. All MAPK inhibitors failed to reverse the effect of either A23187 or PMA on PGDH. The authors conclude that upon stimulation with the same upstream signals, different downstream intracellular pathways regulate PTGS2 and PGDH mRNA expression.

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Authors and Affiliations

  1. Department of Physiology, University of Toronto, Medical Sciences Building, 1 King’s College Circle, M5S 1A8, Toronto, Ontario, Canada

    Valentina Casciani PhD, Alan D. Bocking MD & John R. G. Challis PhD

  2. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Alan D. Bocking MD & John R. G. Challis PhD

  3. Laboratory of Perinatal Medicine and Molecular Biology, Department of Gynecology, Perinatology and Child Health, University “La Sapienza”, Rome, Italy

    Valentina Casciani PhD, Emanuela Marinoni MD, PhD, Massimo Moscarini MD & Romolo Di Iorio MD, PhD

Authors
  1. Valentina Casciani PhD
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  2. Emanuela Marinoni MD, PhD
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  3. Alan D. Bocking MD
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  4. Massimo Moscarini MD
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  5. Romolo Di Iorio MD, PhD
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  6. John R. G. Challis PhD
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Corresponding author

Correspondence to Valentina Casciani PhD.

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The present work was performed at the University of Toronto, Department of Physiology,Toronto, Ontario, Canada.

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Casciani, V., Marinoni, E., Bocking, A.D. et al. Opposite Effect of Phorbol Ester PMA on PTGS2 and PGDH mRNA Expression in Human Chorion Trophoblast Cells. Reprod. Sci. 15, 40–50 (2008). https://doi.org/10.1177/1933719107309647

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