{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:18:31Z","timestamp":1783606711205,"version":"3.55.0"},"reference-count":34,"publisher":"Bioscientifica","issue":"2","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32 HD101384"],"award-info":[{"award-number":["T32 HD101384"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:p>While pregnancy is known to be an inflammatory condition, preeclampsia (PE) is a more extreme state associated with higher cytokines and\/or altered growth factors. It is generally assumed these PE-elevated factors come from stimulation of immune cells and\/or hypoxic uterine tissue, but several studies have shown that endothelial cells may also be a source. The goal of this study was to determine to what extent TNF, a factor overproduced by uteroplacental tissue in PE pregnancy, may influence uterine artery endothelial cells to contribute to these other PE-specific factors in the maternal circulation. Herein, we use multiple analytical methods to show that uterine artery endothelial cells from pregnant sheep (P-UAEC) on exposure to cytokines can secrete multiple cytokines and chemokines seen in PE women, which may contribute to production of Th17 cells and attraction of these and other cells to the vessel surface. Furthermore, the factors not significantly increased by TNF include those known to be specifically secreted by proinflammatory T cells. This begs the question if endothelium itself is the initial primary orchestrator of chemokine and cytokine imbalance, acting directly and indirectly to promote the symptoms of impaired vasodilation and reduced uteroplacental blood flow. If so, future preventive therapies for PE should be targeted at endothelium as well as immune cells.<\/jats:p>","DOI":"10.1530\/jme-25-0008","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T11:41:43Z","timestamp":1754394103000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":3,"title":["TNF but not VEGF induces secretion of multiple chemokines and cytokines by uterine artery endothelial cells: potential implications for preeclampsia"],"prefix":"10.1530","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-6672","authenticated-orcid":true,"given":"L","family":"Clemente","sequence":"first","affiliation":[{"name":"Perinatal Research Laboratories, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin\u2013Madison, 7E Unity Point Health-Meriter Hospital 1 , , ,","place":["Madison, Wisconsin, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona 2 , , ,","place":["Tucson, Arizona, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Chaiyakul","sequence":"additional","affiliation":[{"name":"Department Biostatistics & Medical Informatics, School Medicine and Public Health, University of Wisconsin\u2013Madison 3 , , ,","place":["Madison, Wisconsin, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J H","family":"Adams","sequence":"additional","affiliation":[{"name":"Perinatal Research Laboratories, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin\u2013Madison, 7E Unity Point Health-Meriter Hospital 1 , , ,","place":["Madison, Wisconsin, 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