{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T23:31:10Z","timestamp":1787527870213,"version":"build-2736575974"},"reference-count":43,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T00:00:00Z","timestamp":1569542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neuromedin B (NMB) and its receptor regulate labor onset by mediating inflammatory factors; however the underlying mechanisms remain poorly understood. The present study is aimed to investigate the mechanisms of NMB-induced cyclo-oxygenase 2 (COX-2) expression and interleukin (IL)-6 generation in human primary myometrial cells. The results indicated that NMB could increase phosphorylation of nuclear factor \u03baB (NF-\u03baB) transcription factor p65 (p65) and Jun proto-oncogene, activator protein 1 (AP-1) transcription factor subunit (c-Jun), and in turn, markedly up-regulated the expression levels of COX-2 and IL-6. This up-regulation was significantly attenuated by knockdown of p65 or c-Jun, and enhanced by overexpression of p65 or c-Jun. Furthermore, we identified a potential interaction between p65 and c-Jun following NMB stimulation. In addition, a significant positive correlation was observed between the amount of phosphorylated p65 and the levels of COX-2 and IL-6, and between the amount of phosphorylated c-Jun and COX-2 and IL-6 levels. These data suggested that NMB-induced COX-2 and IL-6 expression were mediated via p65 and c-Jun activation.<\/jats:p>","DOI":"10.1042\/bsr20192139","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T16:54:05Z","timestamp":1568652845000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Neuromedin B mediates IL-6 and COX-2 expression through NF-\u03baB\/P65 and AP-1\/C-JUN activation in human primary myometrial cells"],"prefix":"10.1042","volume":"39","author":[{"given":"Texuan","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiejie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaozhen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingrui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiefeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1633-0587","authenticated-orcid":false,"given":"Weishe","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China"},{"name":"Hunan Engineering Research Center of Early Life Development and Disease Prevention, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,10,11]]},"reference":[{"key":"2021111619504833800_B1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.puhe.2014.03.010","article-title":"Outcomes in preterm infants","volume":"128","author":"Platt","year":"2014","journal-title":"Public Health"},{"key":"2021111619504833800_B2","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/S0140-6736(14)61698-6","article-title":"Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis","volume":"385","author":"Liu","year":"2015","journal-title":"Lancet"},{"key":"2021111619504833800_B3","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1056\/NEJMra050435","article-title":"Prevention of preterm delivery","volume":"357","author":"Simhan","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"2021111619504833800_B4","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1007\/s00404-013-3137-9","article-title":"Tocolysis for preterm labor: expert opinion","volume":"289","author":"Hosli","year":"2014","journal-title":"Arch. Gynecol. Obstet."},{"key":"2021111619504833800_B5","first-page":"579","article-title":"Scanning of drug targets related to uterus contraction from the uterine smooth muscles by cDNA microarray","volume":"32","author":"Zhang","year":"2007","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"2021111619504833800_B6","first-page":"531","article-title":"Expression of NMBR in myometrium in pregnant mice at different gestational ages and its relation with parturition","volume":"34","author":"Zhang","year":"2009","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"2021111619504833800_B7","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1095\/biolreprod.110.085746","article-title":"Neuromedin B and its receptor induce labor onset and are associated with the RELA (NFKB P65)\/IL6 pathway in pregnant mice","volume":"84","author":"Zhang","year":"2011","journal-title":"Biol. Reprod."},{"key":"2021111619504833800_B8","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.bbr.2007.01.021","article-title":"Role of gastrin-releasing peptide and neuromedin B in anxiety and fear-related behavior","volume":"179","author":"Bedard","year":"2007","journal-title":"Behav. Brain Res."},{"key":"2021111619504833800_B9","doi-asserted-by":"publisher","DOI":"10.3390\/cells5010012","article-title":"The regulation of NF-kappaB subunits by phosphorylation","volume":"5","author":"Christian","year":"2016","journal-title":"Cells"},{"key":"2021111619504833800_B10","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/ncb1873","article-title":"WIP1 phosphatase is a negative regulator of NF-kappaB signalling","volume":"11","author":"Chew","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"2021111619504833800_B11","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1093\/molehr\/7.6.581","article-title":"Human labour is associated with nuclear factor-kappaB 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":"2021111619504833800_B12","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1530\/rep.1.00197","article-title":"The role of nuclear factor kappa B in human labour","volume":"130","author":"Lindstrom","year":"2005","journal-title":"Reproduction"},{"key":"2021111619504833800_B13","doi-asserted-by":"publisher","first-page":"e34707","DOI":"10.1371\/journal.pone.0034707","article-title":"Nuclear factor kappa B activation occurs in the amnion prior to labour onset and modulates the expression of numerous labour associated genes","volume":"7","author":"Lim","year":"2012","journal-title":"PLoS ONE"},{"key":"2021111619504833800_B14","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.1096\/fj.13-247783","article-title":"Activator protein 1 is a key terminal mediator of inflammation-induced preterm labor in mice","volume":"28","author":"MacIntyre","year":"2014","journal-title":"FASEB J."},{"key":"2021111619504833800_B15","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1095\/biolreprod67.1.240","article-title":"Differential expression of activator protein-1 transcription factors in pregnant rat myometrium","volume":"67","author":"Mitchell","year":"2002","journal-title":"Biol. Reprod."},{"key":"2021111619504833800_B16","doi-asserted-by":"publisher","first-page":"504952","DOI":"10.1155\/2012\/504952","article-title":"NFkappaB and AP-1 drive human myometrial IL8 expression","volume":"2012","author":"Khanjani","year":"2012","journal-title":"Mediators Inflamm."},{"key":"2021111619504833800_B17","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1210\/jc.2005-2649","article-title":"Regulation of the human oxytocin receptor by nuclear factor-kappaB and CCAAT\/enhancer-binding protein-beta","volume":"91","author":"Terzidou","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2021111619504833800_B18","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.ejogrb.2006.07.024","article-title":"Changes of nuclear factor kappa B (NF-kappaB), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in human myometrium before and during term labor","volume":"132","author":"Choi","year":"2007","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"2021111619504833800_B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1095\/biolreprod.111.095984","article-title":"Neuromedin B and its receptor influence the activity of myometrial primary cells in vitro through regulation of Il6 expression via the Rela\/p65 pathway in mice","volume":"86","author":"Zhang","year":"2012","journal-title":"Biol. Reprod."},{"key":"2021111619504833800_B20","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.mrrev.2009.01.001","article-title":"Translational regulation mechanisms of AP-1 proteins","volume":"682","author":"Vesely","year":"2009","journal-title":"Mutat. Res."},{"key":"2021111619504833800_B21","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/j.bcp.2013.01.013","article-title":"c-Src-dependent MAPKs\/AP-1 activation is involved in TNF-alpha-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells","volume":"85","author":"Yang","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"2021111619504833800_B22","doi-asserted-by":"publisher","first-page":"5488","DOI":"10.1128\/MCB.01657-08","article-title":"Hyperactivated NF-{kappa}B and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells","volume":"29","author":"Ndlovu","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"2021111619504833800_B23","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1111\/j.1432-1033.1994.tb18804.x","article-title":"Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2","volume":"221","author":"Kosaka","year":"1994","journal-title":"Eur. J. Biochem."},{"key":"2021111619504833800_B24","doi-asserted-by":"publisher","first-page":"3355","DOI":"10.1016\/j.bbagen.2013.03.014","article-title":"Endothelin-1 enhances cell migration through COX-2 up-regulation in human chondrosarcoma","volume":"1830","author":"Wu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"2021111619504833800_B25","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1002\/jcp.24795","article-title":"Sphingosine-1-phosphate mediates COX-2 expression and PGE2 \/IL-6 secretion via c-Src-dependent AP-1 activation","volume":"230","author":"Hsu","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"2021111619504833800_B26","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1093\/molehr\/gah194","article-title":"The role of CCAAT\/enhancer-binding protein beta in the transcriptional regulation of COX-2 in human amnion","volume":"11","author":"Lee","year":"2005","journal-title":"Mol. Hum. Reprod."},{"key":"2021111619504833800_B27","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1248\/bpb.b15-00186","article-title":"Fulgidic acid isolated from the rhizomes of Cyperus rotundus suppresses LPS-induced iNOS, COX-2, TNF-alpha, and IL-6 expression by AP-1 inactivation in RAW264.7 macrophages","volume":"38","author":"Shin","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"2021111619504833800_B28","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1248\/bpb.b15-00572","article-title":"Chikusetsusaponin IVa methyl ester isolated from the roots of Achyranthes japonica suppresses LPS-induced iNOS, TNF-alpha, IL-6, and IL-1beta expression by NF-kappaB and AP-1 inactivation","volume":"39","author":"Lee","year":"2016","journal-title":"Biol. Pharm. Bull."},{"key":"2021111619504833800_B29","doi-asserted-by":"publisher","first-page":"3879","DOI":"10.1002\/j.1460-2075.1993.tb06066.x","article-title":"Cross-coupling of the NF-kappa B p65 and Fos\/Jun transcription factors produces potentiated biological function","volume":"12","author":"Stein","year":"1993","journal-title":"EMBO J."},{"key":"2021111619504833800_B30","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1093\/carcin\/bgm293","article-title":"Jun D cooperates with p65 to activate the proximal kappaB site of the cyclin D1 promoter: role of PI3K\/PDK-1","volume":"29","author":"Toualbi-Abed","year":"2008","journal-title":"Carcinogenesis"},{"key":"2021111619504833800_B31","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1053\/j.semperi.2015.07.001","article-title":"Overview of the mechanisms of induction of labor","volume":"39","author":"Irani","year":"2015","journal-title":"Semin. Perinatol."},{"key":"2021111619504833800_B32","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1111\/aogs.12708","article-title":"Role of SOCS3 in the Jak\/stat3 pathway in the human placenta: different mechanisms for preterm and term labor","volume":"94","author":"Zhou","year":"2015","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"2021111619504833800_B33","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1095\/biolreprod.104.032979","article-title":"Human myometrial gene expression before and during parturition","volume":"72","author":"Havelock","year":"2005","journal-title":"Biol. Reprod."},{"key":"2021111619504833800_B34","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2393-13-S1-S7","article-title":"Development and validation of primary human myometrial cell culture models to study pregnancy and labour","volume":"13","author":"Mosher","year":"2013","journal-title":"BMC Pregnancy Childbirth"},{"key":"2021111619504833800_B35","doi-asserted-by":"crossref","first-page":"801","DOI":"10.12891\/ceog2009.2015","article-title":"Interleukin-6 and C-reactive protein levels in the amniotic fluid as indicators of preterm delivery in Turkish women","volume":"42","author":"Oz","year":"2015","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"2021111619504833800_B36","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/S0029-7844(97)00294-9","article-title":"Maternal serum interleukin-6 during pregnancy and during term and preterm labor","volume":"90","author":"Greig","year":"1997","journal-title":"Obstet. Gynecol."},{"key":"2021111619504833800_B37","doi-asserted-by":"publisher","first-page":"51","DOI":"10.17305\/bjbms.2015.1.93","article-title":"Interleukin 6 and fetal fibronectin as a predictors of preterm delivery in symptomatic patients","volume":"15","author":"Hadzi Lega","year":"2015","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"2021111619504833800_B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1530\/rep.0.1240001","article-title":"Prostaglandins and mechanisms of preterm birth","volume":"124","author":"Challis","year":"2002","journal-title":"Reproduction"},{"key":"2021111619504833800_B39","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1093\/carcin\/bgp066","article-title":"Involvement of NF-kappaB and AP-1 in COX-2 upregulation by human papillomavirus 16 E5 oncoprotein","volume":"30","author":"Kim","year":"2009","journal-title":"Carcinogenesis"},{"key":"2021111619504833800_B40","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.bcp.2017.03.003","article-title":"Resveratrol inhibits BK-induced COX-2 transcription by suppressing acetylation of AP-1 and NF-kappaB in human rheumatoid arthritis synovial fibroblasts","volume":"132","author":"Yang","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"2021111619504833800_B41","doi-asserted-by":"publisher","first-page":"ra106","DOI":"10.1126\/scisignal.aac6151","article-title":"Phosphorylation of STAT3 mediates the induction of cyclooxygenase-2 by cortisol in the human amnion at parturition","volume":"8","author":"Wang","year":"2015","journal-title":"Sci. Signal."},{"key":"2021111619504833800_B42","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.ccell.2015.02.004","article-title":"A cytoplasmic NF-kappaB interacting long noncoding RNA blocks IkappaB phosphorylation and suppresses breast cancer metastasis","volume":"27","author":"Liu","year":"2015","journal-title":"Cancer Cell"},{"key":"2021111619504833800_B43","doi-asserted-by":"publisher","first-page":"3492","DOI":"10.1038\/sj.onc.1210133","article-title":"Physical and functional cooperation between AP-1 and beta-catenin for the regulation of TCF-dependent genes","volume":"26","author":"Toualbi","year":"2007","journal-title":"Oncogene"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20192139\/855971\/bsr-2019-2139.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20192139\/855971\/bsr-2019-2139.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T21:39:48Z","timestamp":1664401188000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/39\/10\/BSR20192139\/220474\/Neuromedin-B-mediates-IL-6-and-COX-2-expression"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10,30]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20192139","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,10]]},"published":{"date-parts":[[2019,10]]},"article-number":"BSR20192139"}}