(A) The mRNA levels of mdr1a in bEnd.3 cells treated with HMGB1 plus different inhibitors. Inhibition of TLR4, RAGE, and NF-κB attenuated HMGB1-induced up-regulation of mdr1a mRNA in bEnd.3 cells. LPS-RS: TLR4 antagonist; FPS-ZM1: RAGE inhibitor; SN50: NF-κB nuclear translocation inhibitor. (B&C) The protein levels of P-gp in bEnd.3 cells treated with HMGB1 plus different inhibitors. Representative examples are shown (B) and protein levels were normalized to the cells treated without HMGB1 (C). Inhibition of TLR4, RAGE, and NF-κB attenuated HMGB1-induced up-regulation of P-gp protein in bEnd.3 cells. Data were shown as mean±SD; n = 3. *P<0.05, **P<0.01. HMGB1, high-mobility group box-1; LPS-RS, lipopolysaccharide from Rhodobacter sphaeroides; mdr1a, multidrug resistance1a; NF-κB, nuclear factor-kappa B; P-gp, P-glycoprotein; SD, standard deviation; TLR4, toll-like receptor 4; RAGE, receptor for advanced glycation end products.