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Infection results in elevation of inflammation\u2010related cytokines followed by infiltration of immune cells into gestational tissue. CXCL12\u00a0levels are elevated in preterm birth indicating it may have a role in preterm labour (PTL); however, the pathophysiological correlations between CXCL12\/CXCR4\u00a0signalling and premature labour are poorly understood. In this study, PTL was induced using lipopolysaccharide (LPS) in a murine model. LPS induced CXCL12 RNA and protein levels significantly and specifically in myometrium compared with controls (3\u2010fold and 3.5\u2010fold respectively). Highest levels were found just before the start of labour. LPS also enhanced the infiltration of neutrophils, macrophages and T cells, and induced macrophage M1 polarization. In vitro studies showed that condition medium from LPS\u2010treated primary smooth muscle cells (SMC) induced macrophage migration, M1 polarization and upregulated inflammation\u2010related cytokines such as interleukin (IL)\u20101, IL\u20106 and tumor necrosis factor alpha (TNF\u2010\u03b1). AMD3100 treatment in pregnant mice led to a significant decrease in the rate of PTL (70%), prolonged pregnancy duration and suppressed macrophage infiltration into gestation tissue by 2.5\u2010fold. Further, in\u2010vitro treatment of SMC by AMD3100\u00a0suppressed the macrophage migration, decreased polarization and downregulated IL\u20101, IL\u20106 and TNF\u2010\u03b1 expression. LPS treatment in pregnant mice induced PTL by increasing myometrial CXCL12, which recruits immune cells that in turn produce inflammation\u2010related cytokines. These effects stimulated by LPS were completely reversed by AMD3100 through blocking of CXCL12\/CXCR4\u00a0signalling. Thus, the CXCL12\/CXCR4 axis presents an excellent target for preventing infection and inflammation\u2010related PTL.<\/jats:p>","DOI":"10.1111\/jcmm.17252","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T03:53:16Z","timestamp":1648007596000},"page":"2566-2578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Myometrial\u2010derived CXCL12 promotes lipopolysaccharide induced preterm labour by regulating macrophage migration, polarization and function in mice"],"prefix":"10.1111","volume":"26","author":[{"given":"Lijuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences Yale School of Medicine  New Haven Connecticut 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