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Mol. Hum. Reprod. Advance Access originally published online on March 11, 2008
Molecular Human Reproduction 2008 14(4):215-223; doi:10.1093/molehr/gan008
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© The Author 2008. 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

Prostaglandin F2-alpha receptor regulation in human uterine myocytes

Z. Liang1, S.R. Sooranna2, N. Engineer2, M. Tattersall2, S. Khanjani2, P.R. Bennett3, L. Myatt4 and M.R. Johnson2,5

1Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing 430038, People's Republic of China 2Imperial College Parturition Research Group, Department of Maternal Fetal Medicine, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK 3Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus DuCane Road, London W12 0NN, UK 4Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, 21 Bethesda Avenue, Cincinnati, OH 45267, USA

5 Correspondence address. Tel: +44-20-8846-7892; Fax: +44-20-8846-7796; E-mail: mark.johnson{at}imperial.ac.uk

Investigations of the modulation of prostaglandin F2{alpha} receptor (FP) expression in primary cultures of human uterine myocytes showed that FP mRNA expression was reduced by progesterone, unaltered by cAMP (8-bromo cAMP or forskolin), but increased by the PKA antagonist H89. Interleukin (IL)-1β, tumour necrosis factor-alpha and oxytocin increased FP mRNA expression and IL-6 and prostaglandin E2 reduced FP mRNA expression. The changes in FP protein levels were similar to the mRNA responses. We found that the IL-1β-induced increase in FP expression was mediated at least in part via protein kinase C (PKC), but was independent of mitogen-activated protein kinase, phospholipase C and PI3 kinase. Since IL-1β activates NF{kappa}B, AP-1 and C/EBP, we over-expressed these transcription factors alone and in combination and found that only NF{kappa}B alone increased FP mRNA expression. Finally, we found that the IL-1β-induced increase in FP expression was unaffected by progesterone and/or cAMP, but was accentuated by H89. These data suggest that the pregnancy-induced down-regulation in myometrial FP expression is mediated by progesterone and cAMP and that the increase with labour is induced by inflammatory cytokine activation of PKC and NF{kappa}B.

Key words: Prostaglandin F2{alpha} receptor/labour/progesterone/inflammatory cytokines/NF{kappa}B

Submitted on October 11, 2007; resubmitted on December 15, 2007; accepted on February 6, 2008.


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N. Engineer, S. R. Sooranna, Z. Liang, P. R. Bennett, and M. R. Johnson
Influence of Extracellular Matrix on Cytokine Stimulated Pro-labour Gene Expression in Human Uterine Myocytes
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[Abstract] [PDF]


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