Inhibition of GSK3β decreases the severity of LPS-induced acute lung injury. Mice were given SB216763 (20 mg/kg ip) 14 h and 2 h before intratracheal instillation of saline or LPS (2 mg/kg). A, B, and C show increase in lung wet-to-dry ratios, numbers of bronchoalveolar lavage (BAL) neutrophils, and TNF-α, MIP-2, and total protein concentrations in BAL fluids obtained 24 h after LPS administration. In A, fold increase above values present in mice receiving saline alone are shown (means ± SD, n = 5, *P < 0.05). In B, mean ± SE (n = 5), *P < 0.05, ***P < 0.001 compared with LPS alone, whereas in C, means ± SD (n = 5), *P < 0.05, ***P < 0.001. D: representative Western blots and quantitative data show the levels of HMGB1 and histone 3 (H3) in BAL fluids of control, LPS-treated, and LPS and SB216763-treated mice. Means ± SD (n = 6), *P < 0.05, ***P < 0.001. E and F: Western blots show the amounts of pT172-AMPK, pS79-ACC, pT479-AMPK, total AMPK, and β-actin in lung homogenates from control (saline)-treated mice or 24 h after LPS administration in mice given intratracheal LPS alone or LPS and SB216763 (given ip 14 and 2 h before LPS). Means ± SD (n = 3), *P < 0.05.