{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:10:12Z","timestamp":1790676612158,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,7,9]],"date-time":"2009-07-09T00:00:00Z","timestamp":1247097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p>\n                    <jats:bold>Problem\u2002<\/jats:bold>\n                    Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, pre\u2010eclampsia, and pre\u2010term labor. aPL target the placenta directly by binding to beta\n                    <jats:sub>2<\/jats:sub>\n                    \u2010glycoprotein I (\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Method of study\u2002<\/jats:bold>\n                    First trimester trophoblast cells were treated with anti\u2010\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    GPI monoclonal antibodies and patient\u2010derived aPL, after which cell survival and function was evaluated.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results\u2002<\/jats:bold>\n                    We report that anti\u2010\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    GPI antibodies trigger an inflammatory response in trophoblast, characterized by increased secretion of interleukin (IL)\u20108, MCP\u20101, GRO\u2010\u03b1, and IL\u20101\u03b2, and that this occurs in a TLR\u20104\/MyD88\u2010dependent manner. At high concentrations, these antibodies also induce caspase\u2010mediated cell death. This was attenuated upon disabling of the MyD88 pathway, suggesting that anti\u2010\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    GPI\u2010induced inflammatory mediators compromise trophoblast survival by acting in an autocrine\/paracrine manner. Enhanced IL\u20108, GRO\u2010\u03b1, and IL\u20101\u03b2 secretion also occurred when trophoblast cells were incubated with antibodies from patients with antiphospholipid syndrome. Heparin, which acts as a pro\u2010survival factor in human trophoblast, attenuated the anti\u2010\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    GPI antibody\u2010mediated cell death, and also the pro\u2010inflammatory response, but only at high concentrations.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion\u2002<\/jats:bold>\n                    These findings demonstrate that aPL triggers a placental inflammatory response via the TLR\u20104\/MyD88 pathway, which in turn compromises trophoblast survival. Thus, the TLR\u20104\/MyD88 pathway may provide a new therapeutic target to improve pregnancy outcome in antiphospholipid syndrome patients.\n                  <\/jats:p>","DOI":"10.1111\/j.1600-0897.2009.00717.x","type":"journal-article","created":{"date-parts":[[2009,7,9]],"date-time":"2009-07-09T22:45:20Z","timestamp":1247179520000},"page":"96-111","source":"Crossref","is-referenced-by-count":186,"title":["ORIGINAL ARTICLE: Antiphospholipid Antibodies Induce a Pro\u2010Inflammatory Response in First Trimester Trophoblast Via the TLR4\/MyD88 Pathway"],"prefix":"10.1111","volume":"62","author":[{"given":"Melissa J.","family":"Mulla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J.","family":"Brosens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry 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