Fig. 3.

Inhibition of the p38 mitogen-activated protein (MAP) kinase, but not ERK-1/2, attenuates histamine-induced endothelial barrier disruption. A: histamine causes phosphorylation of the activation sites of both p38 MAP kinase and ERK-1/2 in endothelial cells. Histamine was applied at 10 μM for 2 min. Inhibitors were all applied for 30 min before histamine in the following concentrations: SB203580, 6 μM; PD98059, 10 μM; U0126, 5 μM. VEGF was used as a positive control and was applied for 5 min. The blots shown are representative of three separate experiments. B: time course of 10 μM histamine-induced decreases in transendothelial resistance (TER) in the absence of inhibitors or in the presence of 5 μM U0126, 10 μM PD98059, or 6 μM SB203580. C: maximal change in TER elicited by histamine in the presence of MAPK inhibitors. *P < 0.05 vs. no inhibitors. In B and C, n = 16 HUVEC monolayers in each group.