{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:43:32Z","timestamp":1787013812758,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T00:00:00Z","timestamp":1602806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100011636","name":"March of Dimes Prematurity Research Center Ohio Collaborative","doi-asserted-by":"publisher","award":["6\u2010FY17\u2010295"],"award-info":[{"award-number":["6\u2010FY17\u2010295"]}],"id":[{"id":"10.13039\/100011636","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AI134036\u201001, T32AI095202\u201002"],"award-info":[{"award-number":["1R01AI134036\u201001, T32AI095202\u201002"]}],"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":["F32HD100087"],"award-info":[{"award-number":["F32HD100087"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Problem<\/jats:title>\n                    <jats:p>\n                      Gestational membrane (GM) infection provokes inflammation and can result in preterm prelabor rupture of membranes (PPROM). The choriodecidual layer of the GM includes decidual stromal cells (DSC), cytotrophoblasts (CTB), and macrophages (M\u03c6). Our laboratory has previously shown that DSCs suppress M\u03c6 TNF\u2010\u03b1 production through secreted prostaglandin E\n                      <jats:sub>2<\/jats:sub>\n                      . We hypothesized that CTBs would also inhibit M\u03c6 cytokine expression through secreted mediators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method of Study<\/jats:title>\n                    <jats:p>\n                      THP.1 M\u03c6\u2010like cells with an NF\u2010\u03baB reporter construct or human blood monocyte\u2010derived M\u03c6 were co\u2010cultured with the Jeg3 CTB cell line or primary human CTBs and challenged with group B\n                      <jats:italic>streptococcus<\/jats:italic>\n                      (GBS) or Toll\u2010like receptor (TLR) agonists. Conditioned medium generated from CTB cultures was applied to M\u03c6 cultures before infection or treatment. Alternatively, CTBs were co\u2010incubated with, but physically separated from, M\u03c6 and GBS or TLR\u2010stimulated. NF\u2010\u03baB was assessed via alkaline phosphatase assay, and proinflammatory mediators were assessed by qRT\u2010PCR and ELISA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CTBs suppressed GBS\u2010 or TLR\u2010stimulated M\u03c6 NF\u2010\u03baB activity, and TNF\u2010\u03b1 and MMP9 production. Direct physical contact between CTBs and M\u03c6 was required for full immunosuppression. Immunosuppression could be overcome by increasing the ratio of M\u03c6 to CTB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      CTBs limit M\u03c6 NF\u2010\u03baB activation and production of TNF\u2010\u03b1 and MMP9 through an as\u2010yet unknown, cell\u2010to\u2010cell contact\u2010mediated mechanism. This suppression is distinct from the PGE\n                      <jats:sub>2<\/jats:sub>\n                      \u2010mediated M\u03c6 TNF\u2010\u03b1 suppression by DSC, suggesting that DSCs and CTBs regulate M\u03c6 inflammation through distinct mechanisms. How M\u03c6 integrates these signals in an intact GM will be paramount to determining causes and prevention of PPROM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.13352","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T06:56:02Z","timestamp":1600930562000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cytotrophoblasts suppress macrophage\u2010mediated inflammation through a contact\u2010dependent mechanism"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4296-2916","authenticated-orcid":false,"given":"Alison J.","family":"Eastman","sequence":"first","affiliation":[{"name":"Division of Infectious Disease Department of Medicine Vanderbilt University Medical Center Nashville TN 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