{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:44:30Z","timestamp":1773297870121,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,9,26]],"date-time":"2012-09-26T00:00:00Z","timestamp":1348617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The absence of a fall in circulating progesterone levels has led to the concept that human labour is associated with \u2018functional progesterone withdrawal\u2019 caused through changes in the expression or function of progesterone receptor (<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>). At the time of labour, the human uterus is heavily infiltrated with inflammatory cells, which release cytokines to create a \u2018myometrial inflammation\u2019 <jats:italic>via <\/jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> activation. The negative interaction between <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>, may represent a mechanism to account for \u2018functional progesterone withdrawal\u2019 at term. Conversely, <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> may act to inhibit <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03ba<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> function and so play a role in inhibition of myometrial inflammation during pregnancy. To model this inter\u2010relationship, we have used small interfering (si) <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010mediated knock\u2010down of <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> in human pregnant myocytes and whole genome microarray analysis to identify genes regulated through <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>. We then activated myometrial inflammation using <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 stimulation to determine the role of <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> in myometrial inflammation regulation. Through <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>\u2010knock\u2010down, we found that <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> regulates gene networks involved in myometrial quiescence and extracellular matrix integrity. Activation of myometrial inflammation was found to antagonize <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>\u2010induced gene expression, of genes normally upregulated <jats:italic>via <\/jats:italic><jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>. We found that <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> does not play a role in repression of pro\u2010inflammatory gene networks induced by <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 and that only <jats:styled-content style=\"fixed-case\">MMP10<\/jats:styled-content> was significantly regulated in opposite directions by <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 and <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>. We conclude that progesterone acting through <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> does not generally inhibit myometrial inflammation. Activation of myometrial inflammation does cause \u2018functional progesterone withdrawal\u2019 but only in the context of genes normally upregulated <jats:italic>via <\/jats:italic><jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2012.01567.x","type":"journal-article","created":{"date-parts":[[2012,3,22]],"date-time":"2012-03-22T23:07:01Z","timestamp":1332457621000},"page":"2487-2503","source":"Crossref","is-referenced-by-count":31,"title":["Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes"],"prefix":"10.1111","volume":"16","author":[{"given":"Yun","family":"Lee","sequence":"first","affiliation":[{"name":"Parturition Research Group Imperial College London Institute of Reproductive and Developmental Biology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suren R.","family":"Sooranna","sequence":"additional","affiliation":[{"name":"Parturition Research Group Imperial College London Institute of Reproductive and Developmental Biology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasso","family":"Terzidou","sequence":"additional","affiliation":[{"name":"Parturition Research Group Imperial College London Institute of Reproductive and Developmental Biology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Christian","sequence":"additional","affiliation":[{"name":"Parturition Research Group Imperial College London Institute of Reproductive and Developmental Biology London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Brosens","sequence":"additional","affiliation":[{"name":"Parturition Research Group Imperial College London Institute of Reproductive and Developmental Biology London 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