(A) T24 (left panels) and 5637 (right panels) bladder cancer cells were pretreated with two MEK-specific inhibitors (U0126 10 μM or PD98059 1 μM for 2 h), and subsequently infected with BCG (10 MOI for 8 h). Antimicrobial peptides (HBD-2, HBD-3, and CAMP) in culture supernatants were quantified by ELISA. Data are mean ± SD of 3 independent experiments. *P<0.05 and ** P<0.01, BCG/BCG+PD98059 or BCG/BCG+U0126. Student's T-test. (B) Western blotting analyses showing BCG-induced c-Jun phosphorylation is suppressed by MEK inhibitors in both T-24 and 5637 cells. Cells were pretreated with an MEK-specific inhibitor (U0126; 10 μM, PD98059; 1 μM) for 2 h. Subsequently, the cells were infected with BCG (10 MOI for 48 h) and cell lysates were subjected to Western blot analysis. Phospho-Jun/total Jun expression ratios were determined by densitometric analyses. Expression ratios were normalized to the untreated group. (C) Chromatin immunoprecipitation assay showing that MEK inhibition reduces BCG-mediated AMP release in bladder cancer cells. T24 cells were treated with U0126 (10 μM for 2 hours). The cells were subsequently infected with BCG (10 MOI for 8 hours) and fixed with 10% formaldehyde. The lysates were subject to ChIP assay using anti-c-Jun, -p65, and -Pol II antibodies. Expressions of AMPs were calculated as the ratio of c-Jun, p65, and Pol II to input DNA expression using densitometric analysis. All expression ratios were normalized to the untreated group.