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.

Conclusion: Progesterone can attenuate thrombin-induced BBB disruption by blocking the degradation of TJ proteins and EPCR in bEnd.3 cells.

Keywords: Blood–brain barrier; Endothelial protein C receptor; Progesterone; Thrombin; Tight junction protein; bEnd.3 endothelial cell.