Fig. 3

HMGB1 and thrombin impair BBB integrity. HBMEC monolayers were incubated with HMGB1 (10 ng/ml) and thrombin (Thr, 0.5, 1, or 5 nM) for 3 or 6 h, and BBB integrity was assessed by paracellular permeability to FITC-dextran. a HMGB1 increases luminal to abluminal dextran flux across HBMECs that was reversed by anti-HMGB1 antibody (HMGB1 Ab, 10 ng/ml). The time-dependent increase in HMGB1-induced BBB permeability was shown in the inset. b Exposure to thrombin (3 or 6 h) dose-dependently increases BBB permeability to dextran in HBMECs. c HMGB1 and thrombin disrupt ZO-1 linearity at cell-cell junctions. *p < 0.05, **p < 0.01, and ***p < 0.001 vs. control; ●●●p < 0.01 vs. HMGB1 or HMGB1 + control Ab. N = 5/condition