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Mediators of Inflammation
Volume 2012, Article ID 352807, 9 pages
Research Article

Activation of Peroxisome Proliferator-Activated Receptor by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1

1Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea
2Department of Nursing, Semyung University, Jecheon 390-711, Republic of Korea
3Department of Applied Bioscience, College of Life Science, CHA University, Seongnam 463-712, Republic of Korea

Received 31 August 2012; Revised 27 November 2012; Accepted 29 November 2012

Academic Editor: Kuen-Jer Tsai

Copyright © 2012 Jung Seok Hwang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Peroxisome proliferator-activated receptors (PPARs) are shown to modulate the pathological status of sepsis by regulating the release of high mobility group box 1 (HMGB1), a well-known late proinflammatory mediator of sepsis. Ligand-activated PPARs markedly inhibited lipopolysaccharide- (LPS) induced release of HMGB1 in RAW 264.7 cells. Among the ligands of PPAR, the effect of rosiglitazone, a specific ligand for PPAR , was superior in the inhibition of HMGB1 release induced by LPS. This effect was observed in cells that received rosiglitazone before LPS or after LPS treatment, indicating that rosiglitazone is effective in both treatment and prevention. Ablation of PPAR with small interfering RNA or GW9662-mediated inhibition of PPAR abolished the effect of rosiglitazone on HMGB1 release. Furthermore, the overexpression of PPAR markedly potentiated the inhibitory effect of rosiglitazone on HMGB1 release. In addition, rosiglitazone inhibited LPS-induced expression of Toll-like receptor 4 signal molecules, suggesting a possible mechanism by which rosiglitazone modulates HMGB1 release. Notably, the administration of rosiglitazone to mice improved survival rates in an LPS-induced animal model of endotoxemia, where reduced levels of circulating HMGB1 were demonstrated. Taken together, these results suggest that PPARs play an important role in the cellular response to inflammation by inhibiting HMGB1 release.