{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:39:03Z","timestamp":1792201143854,"version":"4.4.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T00:00:00Z","timestamp":1391472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["DSRR_P24225"],"award-info":[{"award-number":["DSRR_P24225"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Activation of uterine inflammatory pathways leads to preterm labor (PTL), associated with high rates of neonatal mortality and morbidity. The transcription factors nuclear factor \u03baB (NF\u03baB) and activator protein 1 (AP\u20101) regulate key proinflammatory and procontractile genes involved in normal labor and PTL. Here we show that (NF\u03baB) activation normally occurs in the mouse myometrium at gestation day E18, prior to labor, whereas AP\u20101 and JNK activation occurs at labor onset. Where labor was induced using the progesterone receptor antagonist RU486, NFkB and AP\u20101\/JNK activation both occurred at the time of labor (20 h compared to 60 h in DMSO\u2010treated controls). Using an LPS (\n                    <jats:italic>Escherichia coli:<\/jats:italic>\n                    serotype O111)\u2010induced PTL model that selectively activates AP\u20101 but not NFkB, we show that myometrial AP\u20101 activation drives production of cytokines (\n                    <jats:italic>Il\u20106, Il\u20108<\/jats:italic>\n                    , and\n                    <jats:italic>Il\u20101<\/jats:italic>\n                    \u03b2), metalloproteinases (\n                    <jats:italic>Mmp3<\/jats:italic>\n                    and\n                    <jats:italic>Mmp10<\/jats:italic>\n                    ), and procontractile proteins (\n                    <jats:italic>Cox\u20102<\/jats:italic>\n                    and\n                    <jats:italic>Cx43<\/jats:italic>\n                    ) resulting in PTL after 7 h. Protein levels of CX43 and IL\u20101\u03b2, and IL\u20101\u03b2 cleavage, were increased following LPS\u2010induced activation of AP\u20101. Inhibition of JNK by SP600125 (30 mg\/kg) delayed PTL by 6 h (7.5\n                    <jats:italic>vs<\/jats:italic>\n                    . 13.5 h\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). Our data reveal that (NF\u03baB) activation is not a functional requirement for infection\/inflammation\u2010induced preterm labor and that AP\u20101 activation is sufficient to drive inflammatory pathways that cause PTL.\u2014MacIntyre, D. A., Lee, Y. S., Migale, R., Herbert, B. R., Waddington, S. N., Peebles, D., Hagberg, H., Johnson, M. R., Bennett, P. R. Activator protein 1 is a key terminal mediator of inflammation\u2010induced preterm labor in mice.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 28, 2358\u20132368 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-247783","type":"journal-article","created":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T23:00:40Z","timestamp":1391554840000},"page":"2358-2368","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":90,"title":["Activator protein 1 is a key terminal mediator of inflammation\u2010induced preterm labor in mice"],"prefix":"10.1096","volume":"28","author":[{"given":"David A.","family":"MacIntyre","sequence":"first","affiliation":[{"name":"Imperial College Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London Hammersmith Campus London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Imperial College Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London Hammersmith Campus London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Migale","sequence":"additional","affiliation":[{"name":"Imperial College Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London Hammersmith Campus London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwen R.","family":"Herbert","sequence":"additional","affiliation":[{"name":"Imperial College Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London Hammersmith Campus London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon N.","family":"Waddington","sequence":"additional","affiliation":[{"name":"Gene Transfer Technology Group Institute for Women's Health University College London London UK"},{"name":"School of Pathology Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Peebles","sequence":"additional","affiliation":[{"name":"Centre for Perinatal Brain Protection and Repair Institute for Women's Health University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hagberg","sequence":"additional","affiliation":[{"name":"Perinatal Center Department of Clinical Sciences University of Gothenburg Gothenburg Sweden"},{"name":"Centre for the Developing Brain King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Imperial College Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London Hammersmith Campus London UK"},{"name":"Chelsea and Westminster Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip R.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Imperial College Parturition Research Group Institute of Reproduction and Developmental Biology Imperial College London Hammersmith Campus London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0010019"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(99)70400-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/14.1.229"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200008103430601"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-956773"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.1.00197"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401124101"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01069.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034707"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504943200"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01161-9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.5.2327"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"712","DOI":"10.4049\/jimmunol.153.2.712","article-title":"NF-kappa B regulates IL-1 beta transcription through a consensus NF-kappa B binding site and a nonconsensus CRE-like site","volume":"153","author":"Cogswell J. 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