{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:29:11Z","timestamp":1789946951068,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T00:00:00Z","timestamp":1512000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH\/NICHD\u20141R01HD084532\u201001A1"],"award-info":[{"award-number":["NIH\/NICHD\u20141R01HD084532\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03HD067446"],"award-info":[{"award-number":["R03HD067446"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2018,3]]},"abstract":"Problem<\/jats:title>We investigated p38MAPK<\/jats:styled-content> activation\u2010induced fetal membrane cell senescence in response to inflammation (tumour necrosis factor\u2010alpha [TNF<\/jats:styled-content>\u2010\u03b1]) and infection (lipopolysaccharide [LPS<\/jats:styled-content>]), factors associated with spontaneous preterm birth.<\/jats:p><\/jats:sec>Method of study<\/jats:title>Primary amnion epithelial cells (AEC<\/jats:styled-content>s) were exposed to TNF<\/jats:styled-content>\u2010\u03b1, 50\u00a0ng\/mL<\/jats:styled-content> and LPS<\/jats:styled-content>, 100\u00a0ng\/mL<\/jats:styled-content>. Cigarette smoke extract (CSE<\/jats:styled-content>), a known OS<\/jats:styled-content> inducer, was used as positive control. AEC<\/jats:styled-content>s were cotreated with the antioxidant N\u2010acetyl cysteine (NAC<\/jats:styled-content>) and p38MAPK<\/jats:styled-content> inhibitor SB<\/jats:styled-content>203580 to determine the effect of OS<\/jats:styled-content> and p38MAPK<\/jats:styled-content>. Western blot analysis was performed for active (Phospho\u2010p38MAPK<\/jats:styled-content>) and total p38MAPK<\/jats:styled-content>. Senescence was determined by flow cytometry, and culture supernatants were tested for IL<\/jats:styled-content>\u20106 using ELISA.<\/jats:p><\/jats:sec>Results<\/jats:title>TNF<\/jats:styled-content>\u2010\u03b1, but not LPS<\/jats:styled-content>, increased p38MAPK<\/jats:styled-content> activation compared to untreated cells (P<\/jats:italic>\u00a0=\u00a0.01). The number of senescent cells and senescence\u2010associated IL<\/jats:styled-content>\u20106 was higher in both TNF<\/jats:styled-content>\u2010\u03b1 and LPS<\/jats:styled-content>\u2010treated cells compared to control (P<\/jats:italic>\u00a0=\u00a0.001, P<\/jats:italic>\u00a0=\u00a0.01, respectively). Antioxidant NAC<\/jats:styled-content> inhibited p38MAPK<\/jats:styled-content> activation by TNF<\/jats:styled-content>\u2010\u03b1. p38MAPK<\/jats:styled-content> inhibitor SB<\/jats:styled-content>203580 reduced the development of senescence and IL<\/jats:styled-content>\u20106 by TNF<\/jats:styled-content>\u2010\u03b1 and LPS<\/jats:styled-content>. CSE<\/jats:styled-content> treatment validated our current data.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>TNF<\/jats:styled-content>\u2010\u03b1 caused OS\u2010mediated p38MAPK induction, senescence, and IL<\/jats:styled-content>\u20106 increase from AECs. LPS also induced senescence and IL<\/jats:styled-content>\u20106 increase. Inflammatory and infectious factors may cause premature fetal cell senescence contributing to preterm birth pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.12790","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T09:20:45Z","timestamp":1512033645000},"source":"Crossref","is-referenced-by-count":68,"title":["A distinct mechanism of senescence activation in amnion epithelial cells by infection, inflammation, and oxidative stress"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2588-1794","authenticated-orcid":false,"given":"Christopher Luke","family":"Dixon","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of Texas Medical Branch Galveston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of Texas Medical Branch Galveston TX USA"},{"name":"Department of Cell Biology The University of Texas Medical Branch Galveston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Sheller\u2010Miller","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of Texas Medical Branch Galveston TX USA"},{"name":"Department of Biochemistry and Molecular Biology The University of Texas Medical Branch Galveston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Saade","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The University of Texas Medical Branch Galveston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-6105","authenticated-orcid":false,"given":"Ramkumar","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The University 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