title: Progesterone attenuates thrombin-induced endothelial barrier disruption in the brain endothelial cell line bEnd.3: The role of tight junction proteins and the endothelial protein C receptor.
abstract: This study examines the effects of progesterone on blood-brain barrier (BBB) integrity following thrombin administration. Thrombin is expressed in many diseases which affect neural tissue and is associated with breakdown of the BBB. Progesterone has shown protective effects on the BBB in stroke and traumatic brain injury.
  
  
  METHODS
  Mouse brain endothelial (bEnd.3) cells were treated with progesterone (20 μmol/l) for 24h before thrombin administration (60 U/ml). BBB permeability was measured by transendothelial electrical resistance (TEER), because TEER decrease is associated with BBB compromise. Tight junction (TJ) proteins (occludin, claudin-5, and zonula occludens-1) and endothelial protein C receptor (EPCR) were analyzed.
  
  
  RESULTS
  Thrombin decreased TEER and progesterone prevented that decrease. TJ proteins and EPCR were also decreased after thrombin treatment and progesterone treatment blocked that effect.
  
  
  CONCLUSIONS
  Progesterone can attenuate thrombin-induced BBB disruption by blocking the degradation of TJ proteins and EPCR in bEnd.3 cells.
authors: Department of Emergency Medicine, Dongguk University School of Medicine, Goyang-si, Gyeonggi-do, Republic of Korea.
authors: Jeong
authors: J
authors: Hun Lee
authors: Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, GA, USA.
authors: Soonmi
authors: S
authors: Won
authors: Department of Emergency Medicine Brain Research Laboratory, Emory University, Atlanta, GA, USA. Electronic address: dstei04@emory.edu.
authors: Donald G
authors: DG
authors: Stein
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D000074283:Endothelial Protein C Receptor; D051379:Mice; D010539:Permeability; D011374:Progesterone / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D020521:Stroke / Q000378:metabolism; D013917:Thrombin / Q000633:toxicity*; D062725:Tight Junction Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D000074283:Endothelial Protein C Receptor; C080248:Procr protein, mouse; D011956:Receptors, Cell Surface; D062725:Tight Junction Proteins; D011374:Progesterone; D013917:Thrombin
keywords: Blood–brain barrier; Endothelial protein C receptor; Progesterone; Thrombin; Tight junction protein; bEnd.3 endothelial cell