The PI3-Kinase/mTOR-Targeting Drug NVP-BEZ235 Inhibits Growth and IgE-Dependent Activation of Human Mast Cells and Basophils
Figure 8
Effects of NVP-BEZ235 on IgE-mediated histamine release in human BA.
BA obtained from healthy donors (A) or patients allergic to Bet v 1 (B) were preincubated with control medium (Medium Co), various concentrations of NVP-BEZ235 (as indicated), LY294002 (20 µM), or wortmannin (1 µM) at 37°C for 30 minutes. Then, cells were exposed to anti-IgE (1 µg/ml; healthy controls) or recombinant allergen (0.1 µg/ml of Bet v 1; allergic patients) at 37°C for 30 minutes. After centrifugation, histamine concentrations were determined in supernatants and cell-lysates by RIA. Histamine release is expressed as percentage of total histamine. Results represent the mean±S.D. from five donors. Asterisk (*) indicates p<0.05. C: BA obtained from one healthy donor were incubated in control medium (♦-♦) or medium containing NVP-BEZ235, 10 µM (▪-▪) for 30 minutes at 37°C. Then, cells were incubated with various concentrations (as indicated) of anti-IgE (left panel), Ca-ionophore A23187 (middle panel), or recombinant C5a (right panel) for another 30 minutes (37°C). After incubation, supernatants and lysates were harvested and examined for their histamine content. Histamine release was calculated as percent of total histamine. Data are expressed as mean±S.D. of triplicates.