{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:45:30Z","timestamp":1789159530314,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Veterans Affairs","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"Department of Veterans Affairs","award":["BX004256"],"award-info":[{"award-number":["BX004256"]}]},{"name":"Department of Veterans Affairs","award":["RX03958"],"award-info":[{"award-number":["RX03958"]}]},{"name":"Department of Veterans Affairs","award":["TL1 TR001451"],"award-info":[{"award-number":["TL1 TR001451"]}]},{"name":"Department of Veterans Affairs","award":["UL1 TR001450"],"award-info":[{"award-number":["UL1 TR001450"]}]},{"name":"Medical University of South Carolina Obstetrics and Gynecology departmental research funding","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"Medical University of South Carolina Obstetrics and Gynecology departmental research funding","award":["BX004256"],"award-info":[{"award-number":["BX004256"]}]},{"name":"Medical University of South Carolina Obstetrics and Gynecology departmental research funding","award":["RX03958"],"award-info":[{"award-number":["RX03958"]}]},{"name":"Medical University of South Carolina Obstetrics and Gynecology departmental research funding","award":["TL1 TR001451"],"award-info":[{"award-number":["TL1 TR001451"]}]},{"name":"Medical University of South Carolina Obstetrics and Gynecology departmental research funding","award":["UL1 TR001450"],"award-info":[{"award-number":["UL1 TR001450"]}]},{"name":"National Center for Advancing translational Sciences of the National Institutes of Health","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}]},{"name":"National Center for Advancing translational Sciences of the National Institutes of Health","award":["BX004256"],"award-info":[{"award-number":["BX004256"]}]},{"name":"National Center for Advancing translational Sciences of the National Institutes of Health","award":["RX03958"],"award-info":[{"award-number":["RX03958"]}]},{"name":"National Center for Advancing translational Sciences of the National Institutes of Health","award":["TL1 TR001451"],"award-info":[{"award-number":["TL1 TR001451"]}]},{"name":"National Center for Advancing translational Sciences of the National Institutes of Health","award":["UL1 TR001450"],"award-info":[{"award-number":["UL1 TR001450"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Preterm birth and the neonatal pathological sequelae that follow spontaneous preterm labor are closely associated with maternal and fetal inflammatory activation. Previous studies have indicated a role for the complement system in this inflammatory response. Utilizing an LPS inflammation-induced model of preterm birth, we investigated various delivery outcomes and their correlation with complement activation products within cervical, uterine, and fetal brain tissue after administration of LPS. We provide further evidence that complement-mediated inflammation within cervical and uterine tissue contributes to aberrant cellular changes and an increase in preterm delivery. We additionally show that a targeted complement inhibitor that specifically targets to sites of complement activation (CR2-Crry) mitigates the effects of LPS-induced pathology and preterm birth. Complement inhibition increased latency to delivery, mean gestational age at delivery, and average number of viable pups. Furthermore, the improved delivery outcomes seen with CR2-Crry treatment correlated with a reduced inflammatory response in maternal tissue and in fetal brain tissue in terms of reduced complement activation, reduced pro-inflammatory cytokines, and reduced macrophage recruitment. These data indicate that complement inhibition represents a potential therapeutic strategy for preventing preterm birth. The localization of complement inhibition by a site-targeting approach reduces the possibility of unwanted off-target effects.<\/jats:p>","DOI":"10.3390\/cells14141045","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T11:58:07Z","timestamp":1751975887000},"page":"1045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Complement Modulation Mitigates Inflammation-Mediated Preterm Birth and Fetal Neural Inflammation"],"prefix":"10.3390","volume":"14","author":[{"given":"Eliza R.","family":"McElwee","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Hatchell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Alshareef","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Division of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7622-8106","authenticated-orcid":false,"given":"Khalil","family":"Mallah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Hall","sequence":"additional","affiliation":[{"name":"College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Robinson","sequence":"additional","affiliation":[{"name":"College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Eskandari","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Division of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6281-2122","authenticated-orcid":false,"given":"Stephen","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA"},{"name":"Ralph Johnson VA Medical Center, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412831","DOI":"10.1155\/2013\/412831","article-title":"The consequences of chorioamnionitis: Preterm birth and effects on development","volume":"2013","author":"Galinsky","year":"2013","journal-title":"J. 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