title: Increased levels of HMGB1 in trophoblastic debris may contribute to preeclampsia.
abstract: Preeclampsia is triggered by an as yet unknown toxin from the placenta. Antiphospholipid antibodies (aPL), a strong risk factor for preeclampsia, have been shown to induce the production of toxic trophoblastic debris from the placenta. High mobility group box 1 (HMGB1) is a proinflammatory danger signal, and the expression of it has been reported to be increased in preeclampsia. This study examined whether aPL or preeclamptic sera increase the expression of HMGB1 in the syncytiotrophoblast or trophoblastic debris. Trophoblastic debris from normal placental explants that had been cultured with aPL or preeclamptic sera was exposed to endothelial cells. Endothelial cell activation was quantified by cell-surface ICAM-1 expression and U937 monocyte adhesion. The expression of HMGB1 in placental explants and trophoblastic debris that had been treated with aPL or preeclamptic sera was measured by immunohistochemistry and western blotting. The expression of the receptor for advanced glycation end products (RAGE) in endothelial cells was quantified by western blotting. Compared with controls, the expression of HMGB1 in the cytoplasm of the syncytiotrophoblast and trophoblastic debris was increased by treating placental explants with aPL or preeclamptic sera. The increased levels of HMGB1 contributed to endothelial cell activation, mediated in part by the RAGE. Preeclamptic sera and aPL both induced an increase in the cytoplasmic levels of the danger signal HMGB1 in trophoblastic debris. This increased HMGB1 in trophoblastic debris may be one of the toxic factors released from the placenta in preeclampsia.
authors.affiliation: The Hospital of Obstetrics & GynaecologyFudan University, China.|Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
authors.forename: Jun
authors.initials: J
authors.lastname: Shao
authors.affiliation: The Hospital of Obstetrics & GynaecologyFudan University, China q.chen@auckland.ac.nz 34996817@qq.com.|Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
authors.forename: Mancy
authors.initials: M
authors.lastname: Tong
authors.affiliation: Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Wise
authors.affiliation: Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Stone
authors.affiliation: Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chamley
authors.affiliation: The Hospital of Obstetrics & GynaecologyFudan University, China q.chen@auckland.ac.nz 34996817@qq.com.|Department of Obstetrics & GynaecologyThe University of Auckland, New Zealand.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D010920:Placenta / Q000378:metabolism / Q000473:pathology*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human