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The oxytocin receptor antagonist, Atosiban, activates pro-inflammatory pathways in human amnion via Gαi signalling
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Kim, Sung Hye, MacIntyre, David A., Hanyaloglu, Aylin C., Blanks, Andrew M., Thornton, Steven, Bennett, Phillip R. and Terzidou, Vasso (2016) The oxytocin receptor antagonist, Atosiban, activates pro-inflammatory pathways in human amnion via Gαi signalling. Molecular and Cellular Endocrinology, 420 . pp. 11-23. doi:10.1016/j.mce.2015.11.012 ISSN 0303-7207.
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Official URL: http://dx.doi.org/10.1016/j.mce.2015.11.012
Abstract
Oxytocin (OT) plays an important role in the onset of human labour by stimulating uterine contractions and promoting prostaglandin/inflammatory cytokine synthesis in amnion via oxytocin receptor (OTR) coupling. The OTR-antagonist, Atosiban, is widely used as a tocolytic for the management of acute preterm labour. We found that in primary human amniocytes, Atosiban (10 μM) signals via PTX-sensitive Gαi to activate transcription factor NF-κB p65, ERK1/2, and p38 which subsequently drives upregulation of the prostaglandin synthesis enzymes, COX-2 and phospho-cPLA2 and excretion of prostaglandins (PGE2) (n = 6; p < 0.05, ANOVA). Moreover, Atosiban treatment increased expression and excretion of the inflammatory cytokines, IL-6 and CCL5. We also showed that OT-simulated activation of NF-κB, ERK1/2, and p38 and subsequent prostaglandin and inflammatory cytokine synthesis is via Gαi−2 and Gαi−3 but not Gαq, and is not inhibited by Atosiban. Activation or exacerbation of inflammation is not a desirable effect of tocolytics. Therefore therapeutic modulation of the OT/OTR system for clinical management of term/preterm labour should consider the effects of differential G-protein coupling of the OTR and the role of OT or selective OTR agonists/antagonists in activating proinflammatory pathways.
| Item Type: | Journal Article | ||||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Oxytocin -- Research, Cytokines, Prostaglandins, Amnion, Parturition, Childbirth, Premature labor | ||||||||||
| Journal or Publication Title: | Molecular and Cellular Endocrinology | ||||||||||
| Publisher: | Elsevier | ||||||||||
| ISSN: | 0303-7207 | ||||||||||
| Official Date: | 15 January 2016 | ||||||||||
| Dates: |
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| Volume: | 420 | ||||||||||
| Page Range: | pp. 11-23 | ||||||||||
| DOI: | 10.1016/j.mce.2015.11.012 | ||||||||||
| Status: | Peer Reviewed | ||||||||||
| Publication Status: | Published | ||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
| Date of first compliant deposit: | 26 May 2016 | ||||||||||
| Date of first compliant Open Access: | 26 May 2016 | ||||||||||
| Funder: | Action Medical Research (AMR), Genesis Research Trust, National Institute for Health Research (Great Britain) (NIHR), Imperial College Healthcare NHS Trust | ||||||||||
| Grant number: | SP4454 (AMR), P14754 (GRT) |
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