Pharmacological modulation in lung-on-a-chip pulmonary edema model. (A) Administration of Ang-1 (100 ng/ml) prevents fluid leakage caused by IL-2 (1000 U/ml) and Ang-2 (100 ng/ml) applied in conjunction with mechanical stretch. Statistical significance determined for comparison of IL-2 (10% strain) and IL-2 and Ang-1 (10% strain). (B) Immunostaining of epithelial occludin (green) and endothelial VE-cadherin (red) in cell-cell junctions after exposure to cyclic mechanical strain (10% at 0.2 Hz) without IL-2 (control) or with co-administration of IL-2 and Ang-1 for 3 days. Scale bars, 30 μm. (C) Restoration of barrier integrity by Ang-1 treatment assessed by changes in the number and size of intercellular gaps. ***P < 0.001. (D) The effect of TRPV4 inhibitor GSK2193874 (100 nM) on barrier permeability alone and in the presence of IL-2 and 10% strain. Statistical significance determined for comparison of IL-2 alone and IL-2 with GSK inhibitor. For (A, C, and E), data are means ± SEM (n = 3). For (A, C, and E), ***P < 0.001, ANOVA followed by post hoc Tukey’s multiple comparison test.