Imperial College London
Alternate

ProfessorMarkJohnson

Faculty of Medicine, Department 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{Lee:2012:10.1111/j.1582-4934.2012.01567.x,
author = {Lee, Y and Sooranna, SR and Terzidou, V and Christian, M and Brosens, J and Huhtinen, K and Poutanen, M and Barton, G and Johnson, MR and Bennett, PR},
doi = {10.1111/j.1582-4934.2012.01567.x},
journal = {JOURNAL OF CELLULAR AND MOLECULAR MEDICINE},
pages = {2487--2503},
title = {Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes},
url = {http://dx.doi.org/10.1111/j.1582-4934.2012.01567.x},
volume = {16},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The absence of a fall in circulating progesterone levels has led to the concept that human labour is associated with ‘functional progesterone withdrawal’ caused through changes in the expression or function of progesterone receptor (PR). At the time of labour, the human uterus is heavily infiltrated with inflammatory cells, which release cytokines to create a ‘myometrial inflammation’ via NFκB activation. The negative interaction between NFκB and PR, may represent a mechanism to account for ‘functional progesterone withdrawal’ at term. Conversely, PR may act to inhibit NFκB function and so play a role in inhibition of myometrial inflammation during pregnancy. To model this interrelationship, we have used small interfering (si) RNAmediated knockdown of PR in human pregnant myocytes and whole genome microarray analysis to identify genes regulated through PR. We then activated myometrial inflammation using IL1β stimulation to determine the role of PR in myometrial inflammation regulation. Through PRknockdown, we found that PR regulates gene networks involved in myometrial quiescence and extracellular matrix integrity. Activation of myometrial inflammation was found to antagonize PRinduced gene expression, of genes normally upregulated via PR. We found that PR does not play a role in repression of proinflammatory gene networks induced by IL1β and that only MMP10 was significantly regulated in opposite directions by IL1β and PR. We conclude that progesterone acting through PR does not generally inhibit myometrial inflammation. Activation of myometrial inflammation does cause ‘functional progesterone withdrawal’ but only in the context of genes normally upregulated via PR.
AU  - Lee,Y
AU  - Sooranna,SR
AU  - Terzidou,V
AU  - Christian,M
AU  - Brosens,J
AU  - Huhtinen,K
AU  - Poutanen,M
AU  - Barton,G
AU  - Johnson,MR
AU  - Bennett,PR
DO  - 10.1111/j.1582-4934.2012.01567.x
EP  - 2503
PY  - 2012///
SN  - 1582-1838
SP  - 2487
TI  - Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes
T2  - JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
UR  - http://dx.doi.org/10.1111/j.1582-4934.2012.01567.x
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000309237500025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/62145
VL  - 16
ER  -
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