{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:34:34Z","timestamp":1791876874167,"version":"4.3.4"},"reference-count":79,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T00:00:00Z","timestamp":1640908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN-143262"],"award-info":[{"award-number":["FDN-143262"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Prophylactic administration of the broad-spectrum chemokine inhibitor (BSCI) FX125L has been shown to suppress uterine contraction, prevent preterm birth (PTB) induced by Group B Streptococcus in nonhuman primates, and inhibit uterine cytokine\/chemokine expression in a murine model of bacterial endotoxin (LPS)-induced PTB. This study aimed to determine the mechanism(s) of BSCI action on human myometrial smooth muscle cells. We hypothesized that BSCI prevents infection-induced contraction of uterine myocytes by inhibiting the secretion of pro-inflammatory cytokines, the expression of contraction-associated proteins and disruption of myocyte interaction with tissue macrophages. Myometrial biopsies and peripheral blood were collected from women at term (not in labour) undergoing an elective caesarean section. Myocytes were isolated and treated with LPS with\/out BSCI; conditioned media was collected; cytokine secretion was analyzed by ELISA; and protein expression was detected by immunoblotting and immunocytochemistry. Functional gap junction formation was assessed by parachute assay. Collagen lattices were used to examine myocyte contraction with\/out blood-derived macrophages and BSCI. We found that BSCI inhibited (1) LPS-induced activation of transcription factor NF-kB; (2) secretion of chemokines (MCP-1\/CCL2 and IL-8\/CXCL8); (3) Connexin43-mediated intercellular connectivity, thereby preventing myocyte\u2013macrophage crosstalk; and (4) myocyte contraction. BSCI represents novel therapeutics for prevention of inflammation-induced PTB in women.<\/jats:p>","DOI":"10.3390\/cells11010128","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T20:49:38Z","timestamp":1641242978000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Broad-Spectrum Chemokine Inhibitor Blocks Inflammation-Induced Myometrial Myocyte\u2013Macrophage Crosstalk and Myometrial Contraction"],"prefix":"10.3390","volume":"11","author":[{"given":"Adam","family":"Boros-Rausch","sequence":"first","affiliation":[{"name":"Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Suite 6-1017, Toronto, ON M5G 1X5, Canada"},{"name":"Department of Physiology, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-8156","authenticated-orcid":false,"given":"Oksana","family":"Shynlova","sequence":"additional","affiliation":[{"name":"Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Suite 6-1017, Toronto, ON M5G 1X5, Canada"},{"name":"Department of Physiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen James","family":"Lye","sequence":"additional","affiliation":[{"name":"Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Suite 6-1017, Toronto, ON M5G 1X5, Canada"},{"name":"Department of Physiology, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00281-020-00807-y","article-title":"Pathogenesis of Preterm Birth: Bidirectional Inflammation in Mother and Fetus","volume":"42","author":"Green","year":"2020","journal-title":"Semin. 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