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PDE4 inhibition prevents preterm delivery induced by an intrauterine inflammation.

Abstract : The aim of this study was to explore the anti-inflammatory properties of phosphodiesterase-4 (PDE4) inhibitors in vivo and their potential ability to prevent inflammation-induced preterm delivery. Indeed, intrauterine inflammation is the major etiology of very preterm delivery, the leading cause of neonatal mortality and morbidity. Intrauterine injection of Escherichia coli LPS in 15-day-pregnant mice induced an increase of PDE4 activity and PDE4B expression at the maternofetal interface, a rise of amniotic fluid levels of TNF-alpha, IL-1beta, IL-6, and IL-10 and provoked massive preterm delivery and fetal demise. Selective PDE4 inhibition by rolipram prevented the rise in the proinflammatory cytokines. Following the nuclear translocation of the transcription factor NFkappaB, as a marker of cellular activation after the inflammatory challenge, showed a time-dependent sequential activation of the gestational tissues, from the uterine mesometrial to the fetal compartment, particularly in the glycogen-trophoblastic cells of the placenta. This activation was disrupted by PDE4 inhibition, and inflammation-induced preterm delivery and fetal demise were prevented. PDE4 selective inhibitors may thus represent a novel effective treatment to delay inflammation-induced preterm delivery and to prevent adverse outcomes in infants.
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https://www.hal.inserm.fr/inserm-00112464
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Submitted on : Tuesday, October 28, 2008 - 11:04:57 AM
Last modification on : Tuesday, September 22, 2020 - 3:38:51 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 9:55:41 PM

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  • HAL Id : inserm-00112464, version 1
  • PRODINRA : 250295
  • PUBMED : 17202375

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Thomas Schmitz, Evelyne Souil, Roxane Hervé, Carole Nicco, Frédéric Batteux, et al.. PDE4 inhibition prevents preterm delivery induced by an intrauterine inflammation.. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2007, 178 (2), pp.1115-21. ⟨inserm-00112464⟩

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