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The precise upstream biochemical pathways that regulate the transition between uterine quiescence during pregnancy and contractility during labor remain unclear. It is well known however that intrauterine inflammation, including infection, is commonly associated with preterm labor. In this study, we identified the immunoproteasome subunit low\u2010molecular\u2010mass protein (LMP)7 mRNA expression to be significantly upregulated in laboring human myometrium. Silencing LMP7 using siRNA\u2010targeted knockdown of LMP7 and its inhibitor ONX\u20100914 in human myometrial cells and tissues decreased proinflammatory cytokines (IL\u20106), cell chemotaxis (CXCL8, CCL2 expression, and THP\u20101 migration), cell to cell adhesion (ICAM1 expression and myometrial adhesion), contraction\u2010associated proteins (PTGS2, FP, PGE2, and PGF2\u03b1), as well as suppressing contractions in myometrial cells and in myometrial tissues obtained from laboring women. In addition, LMP7 silencing reduced NF\u2010\u03baB RelA activity. ONX\u20100914 alleviated inflammation (CCL3, CXCL1, PTGS2, and IL\u20106) in myometrium, placenta, fetal brain, amniotic fluid, and maternal serum induced by LPS in pregnant mice. Collectively, our data suggest a novel role for ONX\u2010014 to suppress uterine activation and contractility associated with preterm labor.<\/jats:p>","DOI":"10.1002\/eji.201747458","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T19:31:00Z","timestamp":1528486260000},"page":"1350-1363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The immunoproteasome inhibitor ONX\u20100914 regulates inflammation and expression of contraction associated proteins in myometrium"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-858X","authenticated-orcid":false,"given":"Stella","family":"Liong","sequence":"first","affiliation":[{"name":"Obstetrics, Nutrition, and Endocrinology Group Department of Obstetrics and Gynaecology University of Melbourne Victoria Australia"},{"name":"Mercy Perinatal Research Centre Mercy Hospital for Women Heidelberg Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratana","family":"Lim","sequence":"additional","affiliation":[{"name":"Obstetrics, Nutrition, and Endocrinology Group Department of Obstetrics and Gynaecology University of Melbourne Victoria Australia"},{"name":"Mercy Perinatal Research Centre Mercy Hospital for Women Heidelberg Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn","family":"Nguyen\u2010Ngo","sequence":"additional","affiliation":[{"name":"Obstetrics, Nutrition, and Endocrinology Group Department of Obstetrics and Gynaecology University of Melbourne Victoria Australia"},{"name":"Mercy Perinatal Research Centre Mercy Hospital for Women Heidelberg Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian","family":"Barker","sequence":"additional","affiliation":[{"name":"Obstetrics, Nutrition, and Endocrinology Group Department of Obstetrics and Gynaecology University of Melbourne Victoria Australia"},{"name":"Mercy Perinatal Research Centre Mercy Hospital for Women Heidelberg Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena C.","family":"Parkington","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biomedicine Discovery Institute Monash University Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Lappas","sequence":"additional","affiliation":[{"name":"Obstetrics, Nutrition, and Endocrinology Group Department of Obstetrics and Gynaecology University of Melbourne Victoria Australia"},{"name":"Mercy Perinatal Research Centre Mercy Hospital for Women Heidelberg Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,28]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Born too soon: The global action report on preterm birth","author":"March of Dimes, P., Save the Children, WHO","year":"2012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60560-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.90690"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2010.09.011"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61577-8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)71048-5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60074-4"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2008.04.002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1521-6934(03)00069-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod67.2.668"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2006.05.011"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.1.00197"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.3.1033-1041.2002"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12229"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12366"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22368"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.018481"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1978"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.03.117"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903182"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201303543"},{"key":"e_1_2_7_23_1","first-page":"469","article-title":"Cellular\u2010distribution of proteasome subunit Lmp7 messenger\u2010RNA and protein in human placentas","volume":"86","author":"Roby K. 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