Reactive astrocytes increase the expression of P-gp and Mrp1 via TNF-α and NF-κB signaling.

To understand multidrug resistance gene expression in reactive astrocytes, the present study involved stimulated astrocytes with tumor necrosis factor (TNF)-α and determined gene expression by reverse transcription-quantitative polymerase chain reaction and western blot analysis. Stimulation induced P-glycoprotein (gp) and multidrug resistance-associated protein (MRP0) 1 expression, which peaked by 24 h. Interestingly, the expression of P-gp and Mrp1 correlated with cell proliferation. Therefore, reactivation of astrocytes may increase P-gp and Mrp1 expression through TNF-α and nuclear factor (NF)-κB signaling. To the best of the authors' knowledge, the present study is the first to demonstrate that in vitro activated astrocytes likely induced P-gp and Mrp1 expression by increasing NF-κB expression. The results of the present study provide a novel insight into the mechanism of refractory epilepsy and suggest inhibiting cytokine signaling may block multidrug resistance. [ABSTRACT FROM AUTHOR]