{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:06:53Z","timestamp":1792390013680,"version":"4.4.0"},"reference-count":28,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:p>Both human preterm labor (PTL) and term labor are consistently associated with a chemokine-induced inflammatory infiltration of the myometrium. However, what regulates myometrial chemokine expression and whether the increase in expression precedes the onset of labor, and so may have a role in its causation, or occurs after, and is simply a consequence of labor, is uncertain. Therefore, we assessed 1) chemokine expression in nonlaboring and laboring myometrial samples obtained at and before term and 2) the factors that regulate myometrial chemokine expression. We found that term labor was characterized by an increase in CXCL8 and CCL2 in both upper and lower segments, whereas PTL was associated with a distinct pattern of chemokine expression, with increases in CCL5, CXCL5, and CCL20 in the lower segment myometrium only. Further, we found that chemokine expression in myometrial cell cultures was increased by stretch and inflammatory cytokines and reduced by prostglandins and oxytocin and that the primary mediator of stretch and cytokine effects was nuclear factor \u03baB (NF-\u03baB) and to a lesser extent MAPK. These data show that PTL appears to be associated with a distinct pattern of chemokine expression, that stretch and cytokines both drive myometrial chemokine expression primarily via activation of NF-\u03baB. These data suggest that the modulation of NF-\u03baB activity may be of potential benefit in the management of PTL.<\/jats:p>","DOI":"10.1210\/en.2011-1506","type":"journal-article","created":{"date-parts":[[2011,11,2]],"date-time":"2011-11-02T02:51:08Z","timestamp":1320202268000},"page":"481-491","source":"Crossref","is-referenced-by-count":74,"title":["Stretch and Inflammatory Cytokines Drive Myometrial Chemokine Expression Via NF-\u03baB Activation"],"prefix":"10.1210","volume":"153","author":[{"given":"Renyi","family":"Hua","sequence":"first","affiliation":[{"name":"Imperial College Parturition Research Group (R.H., S.R.S., P.R.B., M.R.J.), Academic Department of Obstetrics and Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Pease","sequence":"first","affiliation":[{"name":"Leukocyte Biology Section (J.E.P., J.M.V.), National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suren R.","family":"Sooranna","sequence":"first","affiliation":[{"name":"Imperial College Parturition Research Group (R.H., S.R.S., P.R.B., M.R.J.), Academic Department of Obstetrics and Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Viney","sequence":"first","affiliation":[{"name":"Leukocyte Biology Section (J.E.P., J.M.V.), National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Nelson","sequence":"first","affiliation":[{"name":"Centre for Population and Health Sciences (S.M.N.), University of Glasgow, Glasgow G11 6NT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Les","family":"Myatt","sequence":"first","affiliation":[{"name":"Center for Pregnancy and Newborn Research (L.M.), University of Texas Health Science Center San Antonio, San Antonio, Texas 78229-3900"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip R.","family":"Bennett","sequence":"first","affiliation":[{"name":"Imperial College Parturition Research Group (R.H., S.R.S., P.R.B., M.R.J.), Academic Department of Obstetrics and Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Johnson","sequence":"first","affiliation":[{"name":"Imperial College Parturition Research Group (R.H., S.R.S., P.R.B., M.R.J.), Academic Department of Obstetrics and Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612395327700_B1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.siny.2004.04.002","article-title":"Epidemiology of preterm birth and neonatal outcome.","volume":"9","author":"Wen","year":"2004","journal-title":"Semin Fetal Neonatal Med"},{"key":"2020071612395327700_B2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/humrep\/14.1.229","article-title":"Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process.","volume":"14","author":"Thomson","year":"1999","journal-title":"Hum Reprod"},{"key":"2020071612395327700_B3","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1006\/scdb.2000.0158","article-title":"Uterine leukocytes: key players in pregnancy.","volume":"11","author":"Hunt","year":"2000","journal-title":"Semin Cell Dev Biol"},{"key":"2020071612395327700_B4","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1053\/plac.2002.0948","article-title":"Cytokines, prostaglandins and parturition\u2014a review.","volume":"24","author":"Keelan","year":"2003","journal-title":"Placenta"},{"key":"2020071612395327700_B5","doi-asserted-by":"crossref","first-page":"104.e1","DOI":"10.1016\/j.ajog.2008.08.032","article-title":"Term labor is associated with a core inflammatory response in human fetal membranes, myometrium, and cervix.","volume":"200","author":"Bollapragada","year":"2009","journal-title":"Am J Obstet Gynecol"},{"key":"2020071612395327700_B6","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1034\/j.1600-0897.2002.01075.x","article-title":"Uterine chemokines in reproductive physiology and pathology.","volume":"47","author":"Kayisli","year":"2002","journal-title":"Am J Reprod Immunol"},{"key":"2020071612395327700_B7","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/S0002-9378(99)70337-6","article-title":"A role for the novel cytokine RANTES in pregnancy and parturition.","volume":"181","author":"Athayde","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"2020071612395327700_B8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1080\/14767050500141329","article-title":"Monocyte chemotactic protein-1 is increased in the amniotic fluid of women who deliver preterm in the presence or absence of intra-amniotic infection.","volume":"17","author":"Esplin","year":"2005","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2020071612395327700_B9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1515\/JPM.2008.034","article-title":"Exodus-1 (CCL20): evidence for the participation of this chemokine in spontaneous labor at term, preterm labor, and intrauterine infection.","volume":"36","author":"Hamill","year":"2008","journal-title":"J Perinat Med"},{"key":"2020071612395327700_B10","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1600-0897.2008.00620.x","article-title":"CXCL6 (granulocyte chemotactic protein-2): a novel chemokine involved in the innate immune response of the amniotic cavity.","volume":"60","author":"Mittal","year":"2008","journal-title":"Am J Reprod Immunol"},{"key":"2020071612395327700_B11","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/j.1582-4934.2010.01069.x","article-title":"NF-\u03baB regulates a cassette of immune\/inflammatory genes in human pregnant myometrium at term.","volume":"15","author":"Khanjani","year":"2011","journal-title":"J Cell Mol Med"},{"key":"2020071612395327700_B12","first-page":"209A","article-title":"Monocyte chemoattractant protein-1 integrates mechanical and endocrine signals that mediate term and preterm labour.","volume":"14","author":"Shynlova","year":"2007","journal-title":"Reprod Sci"},{"key":"2020071612395327700_B13","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1177\/1933719107307792","article-title":"Modulation of monocyte chemotactic protein-1 expression during lipopolysaccharide-induced preterm delivery in the pregnant mouse.","volume":"14","author":"Diamond","year":"2007","journal-title":"Reprod Sci"},{"key":"2020071612395327700_B14","doi-asserted-by":"crossref","first-page":"42957","DOI":"10.1074\/jbc.M103933200","article-title":"The CC chemokine eotaxin (CCL11) is a partial agonist of CC chemokine receptor 2b.","volume":"276","author":"Martinelli","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071612395327700_B15","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1002\/eji.200324235","article-title":"Molecular characterization of the chemokine receptor CXCR3: evidence for the involvement of distinct extracellular domains in a multi-step model of ligand binding and receptor activation.","volume":"33","author":"Xanthou","year":"2003","journal-title":"Eur J Immunol"},{"key":"2020071612395327700_B16","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1210\/jc.2004-0277","article-title":"Mechanical stretch up-regulates the human oxytocin receptor in primary human uterine myocytes.","volume":"90","author":"Terzidou","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612395327700_B17","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.1210\/jc.2004-1390","article-title":"The mitogen-activated protein kinase dependent expression of prostaglandin H synthase-2 and interleukin-8 messenger ribonucleic acid by myometrial cells: the differential effect of stretch and interleukin-1\u03b2.","volume":"90","author":"Sooranna","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612395327700_B18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1084\/jem.187.1.129","article-title":"Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.","volume":"187","author":"Bonecchi","year":"1998","journal-title":"J Exp Med"},{"key":"2020071612395327700_B19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1371\/journal.pcbi.0010019","article-title":"Inflammatory aetiology of human myometrial activation tested using directed graphs.","volume":"1","author":"Bisits","year":"2005","journal-title":"PLoS Comput Biol"},{"key":"2020071612395327700_B20","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1530\/REP-07-0461","article-title":"Pro-labour myometrial gene expression: are preterm labour and term labour the same?","volume":"135","author":"Tattersall","year":"2008","journal-title":"Reproduction"},{"key":"2020071612395327700_B21","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/molehr\/7.6.581","article-title":"Human labour is associated with nuclear factor-\u03baB activity which mediates cyclo-oxygenase-2 expression and is involved with the \u2018functional progesterone withdrawal.\u2019","volume":"7","author":"Allport","year":"2001","journal-title":"Mol Hum Reprod"},{"key":"2020071612395327700_B22","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1210\/me.2005-0242","article-title":"Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-\u03baB may contribute to the onset of labor through inhibition of PR function.","volume":"20","author":"Condon","year":"2006","journal-title":"Mol Endocrinol"},{"key":"2020071612395327700_B23","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1093\/molehr\/gah112","article-title":"Mechanical stretch of human uterine smooth muscle cells increases IL-8 mRNA expression and peptide synthesis.","volume":"10","author":"Loudon","year":"2004","journal-title":"Mol Hum Reprod"},{"key":"2020071612395327700_B24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/molehr\/gah021","article-title":"Mechanical stretch activates type 2 cyclooxygenase via activator protein-1 transcription factor in human myometrial cells.","volume":"10","author":"Sooranna","year":"2004","journal-title":"Mol Hum Reprod"},{"key":"2020071612395327700_B25","doi-asserted-by":"crossref","first-page":"E686","DOI":"10.1152\/ajpendo.90263.2008","article-title":"Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men.","volume":"295","author":"Clodi","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020071612395327700_B26","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1186\/1471-2393-7-S1-S12","article-title":"PDE4 as a target in preterm labour.","volume":"7","author":"Mehats","year":"2007","journal-title":"BMC Pregnancy Childbirth"},{"key":"2020071612395327700_B27","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1600-0897.2009.00773.x","article-title":"Can sulfasalazine prevent infection-mediated pre-term birth in a murine model?","volume":"63","author":"Nath","year":"2010","journal-title":"Am J Reprod Immunol"},{"key":"2020071612395327700_B28","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1210\/en.2008-1178","article-title":"The cyclopentenone 15-deoxy-\u03b4 12,14-prostaglandin J(2) delays lipopolysaccharide-induced preterm delivery and reduces mortality in the newborn mouse.","volume":"150","author":"Pirianov","year":"2009","journal-title":"Endocrinology"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/153\/1\/481\/10388976\/endo0481.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/153\/1\/481\/10388976\/endo0481.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T21:26:47Z","timestamp":1594934807000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/153\/1\/481\/2424501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,1]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2011-1506","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,1]]}}}