Activation of Peroxisome Proliferator-Activated Receptor by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1
Figure 6
Rosiglitazone prevents endotoxin lethality by attenuating HMGB1 release in vivo. (a) BALB/c mice ( per group) were injected with a single dose of rosiglitazone (10 mg/kg, i.p.) with or without GW9662 (1 mg/kg, i.p.), followed 30 min later by a lethal infusion of endotoxin (LPS, 10 mg/kg, i.p.). (b) BALB/c mice ( per group) infused with endotoxin (LPS, 10 mg/kg, i.p.) were treated with rosiglitazone (10 mg/kg, i.p.) 0, 1, 3, 6, and 12 h later. Survival was monitored daily for up to 2 weeks. (c) In a parallel group of rosiglitazone-administered mice, circulating levels of HMGB1 were detected by Western blot analysis using sera prepared from samples collected at 20 h post-LPS injection. Representative blots from four independent experiments and densitometric measurements are shown. Ponceau S staining was used as a loading control. The results are expressed as the means S.E. (). compared to the untreated group; compared to the LPS-treated group; compared to the LPS plus rosiglitazone-treated group.
