Imperial College London

ProfessorMarkJohnson

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Clinical Chair in Obstetrics
 
 
 
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Contact

 

+44 (0)20 3315 7887mark.johnson

 
 
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Location

 

H3.35Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Herbert:2019:biolre/ioz112,
author = {Herbert, BR and Markovic, D and Georgiou, E and Lai, PF and Singh, N and Yulia, A and Johnson, MR},
doi = {biolre/ioz112},
journal = {Biology of Reproduction},
pages = {813--822},
title = {Aminophylline and progesterone prevent inflammation-induced preterm parturition in the mouse},
url = {http://dx.doi.org/10.1093/biolre/ioz112},
volume = {101},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Although progesterone (P4) supplementation is the most widely used therapy for the prevention of preterm labor (PTL), reports of its clinical efficacy have been conflicting. We have previously shown that the anti-inflammatory effects of P4 can be enhanced by increasing intracellular cAMP levels in primary human myometrial cells. Here we have examined whether adding aminophylline (Am), a non-specific phosphodiesterase (PDE) inhibitor that increases intracellular cyclic adenosine monophosphate (cAMP) levels, to P4 might improve its efficacy using in vivo and in vitro models of PTL. In a mouse model of lipopolysaccharide (LPS)-induced PTL, we found that the combination of P4 and Am delayed the onset of LPS-induced PTL, while the same dose of P4 and Am alone had no effect. Pup survival was not improved by either agent alone or in combination. Myometrial prolabor and inflammatory cytokine gene expression was reduced, but the reduction was similar in P4 and P4/Am treated mice. There was no effect of the combination of P4 and Am on an ex vivo assessment of myometrial contractility. In human myometrial cells and myometrial tissue explants, we found that the combination had marked anti-inflammatory effects, reducing cytokine and COX-2 mRNA and protein levels to a greater extent than either agent alone. These data suggest that the combination of P4 and Am has a more potent anti-inflammatory effect than either agent alone and may be an effective combination in women at high-risk of PTL.
AU - Herbert,BR
AU - Markovic,D
AU - Georgiou,E
AU - Lai,PF
AU - Singh,N
AU - Yulia,A
AU - Johnson,MR
DO - biolre/ioz112
EP - 822
PY - 2019///
SN - 1529-7268
SP - 813
TI - Aminophylline and progesterone prevent inflammation-induced preterm parturition in the mouse
T2 - Biology of Reproduction
UR - http://dx.doi.org/10.1093/biolre/ioz112
UR - https://www.ncbi.nlm.nih.gov/pubmed/31295341
UR - https://academic.oup.com/biolreprod/article/101/4/813/5531303
UR - http://hdl.handle.net/10044/1/71480
VL - 101
ER -