Lipopolysaccharide-activated microglia lower P-glycoprotein function in brain microvascular endothelial cells

► In an RBEC monolayer, LPS showed no effect on P-gp function. ► In the presence of microglia, LPS lowered P-gp function in RBECs. ► LPS-activated microglia induced P-gp dysfunction without altering its expression. ► An NADPH oxidase inhibitor reversed this effect of LPS-activated microglia. ► The decrease in P-gp activity in RBECs may be mediated by the NADPH oxidase pathway.