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Mol. Hum. Reprod. Advance Access originally published online on February 2, 2006
Molecular Human Reproduction 2006 12(2):89-97; doi:10.1093/molehr/gal005
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. for Permissions, please email: journals.permissions@oxfordjournals.org

Anti-inflammatory and relaxatory effects of prostaglandin E2 in myometrial smooth muscle

Donna M. Slater1,2,5, Shirley Astle1, Nicola Woodcock1, Joanna E. Chivers3, Norbert C.J. de Wit1, Steven Thornton4, Manu Vatish4 and Robert Newton2

1Department of Biological Sciences, Biomedical Research Institute, University of Warwick, Coventry, UK, 2Faculty of Medicine, University of Calgary, Alberta, Canada, 3Thoracic Medicine, National Heart and Lung Institute, Imperial College London, London and 4Warwick Medical School, University of Warwick, Coventry, UK

5 To whom correspondence should be addressed at: Department of Biological Sciences, Biomedical Research Institute, University of Warwick, Coventry CV4 7AL, UK. E-mail: d.m.slater{at}warwick.ac.uk

The onset of human labour is complex and involves multiple mediators, prostaglandins, cytokines and chemokines. However, whilst prostaglandins are routinely used for labour induction and inhibitors of prostaglandin synthesis are used to prevent pre-term labour, these practices are not invariably successful, and the rationale for their use is equivocal. As COX-2 and prostaglandin E2 (PGE2) production is increased towards term, we have investigated the effect of PGE2 and other cAMP-elevating agents on events associated with labour induction. Time-dependent increases in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-8 (IL-8) release were observed following treatment of primary human myometrial smooth muscle (HMSM) cells with IL-1ß, via mechanisms that required de novo transcription and translation. Prior treatment with PGE2 (1 µM) produced 86 and 80% decreases in GM-CSF and IL-8 release, respectively. Similarly, the cAMP analogue, 8-bromo-cAMP (8Br-cAMP) and the phosphodiesterase-4 (PDE4) inhibitor, rolipram, also repressed GM-CSF and IL-8 release. In addition, PGE2, 8Br-cAMP, rolipram and salbutamol all had a dose-dependent inhibitory effect on spontaneous myometrial contractions in vitro. In this study, PGE2 reduced the release of factors associated with cervical ripening and attenuated force development in myometrial smooth muscle, raising the possibility that in myometrium, PGE2 may act to down-regulate some of the processes that contribute to the onset of human labour and may be beneficial in helping to maintain pregnancy towards term.

Key words: contractility/cytokine/myometrial smooth muscle/prostaglandins


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S. Astle, R. Newton, S. Thornton, M. Vatish, and D.M. Slater
Expression and regulation of prostaglandin E synthase isoforms in human myometrium with labour
Mol. Hum. Reprod., January 1, 2007; 13(1): 69 - 75.
[Abstract] [Full Text] [PDF]


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