PI3K inhibition augments Mtb-driven macrophage MMP-1 secretion.

<p><b>A.</b> Global inhibition of the PI3K kinase pathway with LY294002 significantly increases macrophage MMP-1 secretion at 72h. <b>B.</b> PI3K inhibition increases macrophage MMP-1 gene expression at 24 h. <b>C.</b> Targeted inhibition of PI3Kδ with IC87114 similarly increases MMP-1 secretion at 72h. <b>D.</b> Increased secretion with IC87114 is secondary to increased mRNA accumulation at 24h. <b>E.</b> Mtb infection increases AKT phosphorylation from 30 minutes, peaking at 60 minutes and declining after 4 h. AKT phosphorylation is completely inhibited by LY294002 at 30 minutes and 4 h. <b>F.</b> Targeted inhibition of PI3K / PDK1 with NVP-BAG956 also increases MMP-1 secretion at 72h. Data show mean and standard deviation of experiments performed in triplicate and are representative of experiments performed on a minimum of three occasions. P values are Student’s t-test.