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Activation of peroxisome proliferator-activated receptor γ by rosiglitazone inhibits lipopolysaccharide-induced release of high mobility group box 1.

Hwang JS, Kang ES, Ham SA, Yoo T, Lee H, Paek KS, Park C, Kim JH, Lim DS, Seo HG - Mediators Inflamm. (2012)

Bottom Line: Among the ligands of PPAR, the effect of rosiglitazone, a specific ligand for PPARγ, was superior in the inhibition of HMGB1 release induced by LPS.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.

ABSTRACT
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 PPARγ, 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 PPARγ with small interfering RNA or GW9662-mediated inhibition of PPARγ abolished the effect of rosiglitazone on HMGB1 release. Furthermore, the overexpression of PPARγ 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.

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Related in: MedlinePlus

Rosiglitazone inhibits Poly (I:C)-induced HMGB1 release in RAW 264.7 cells. (a) Cells grown to 60% confluency were incubated with serum-free medium for 24 h and then stimulated with LPS and/or Poly (I:C) in the presence or absence of rosiglitazone for 24 h. Equal volumes of conditioned media were subjected to Western blot analysis for the detection of HMGB1. Ponceau S staining was used as a loading control. (b) At the same time, total protein was extracted, fractioned by electrophoresis, and immunoblotted with the indicated antibodies. The results shown are representative of three independent experiments.
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fig2: Rosiglitazone inhibits Poly (I:C)-induced HMGB1 release in RAW 264.7 cells. (a) Cells grown to 60% confluency were incubated with serum-free medium for 24 h and then stimulated with LPS and/or Poly (I:C) in the presence or absence of rosiglitazone for 24 h. Equal volumes of conditioned media were subjected to Western blot analysis for the detection of HMGB1. Ponceau S staining was used as a loading control. (b) At the same time, total protein was extracted, fractioned by electrophoresis, and immunoblotted with the indicated antibodies. The results shown are representative of three independent experiments.

Mentions: To examine whether rosiglitazone has a specific effect against LPS stimulation in the inhibition of HMGB1 release, RAW 264.7 cells were stimulated with Poly (I:C), a well-known ligand of Toll-like receptor (TLR) 3, in the presence or absence of rosiglitazone for 24 h. Rosiglitazone significantly inhibited Poly (I:C)-induced HMGB1 release, but not affect expression levels of HMGB1 (Figure 2), indicating that effect of rosiglitazone on the inhibition of HMGB1 release is not limited to the LPS.


Activation of peroxisome proliferator-activated receptor γ by rosiglitazone inhibits lipopolysaccharide-induced release of high mobility group box 1.

Hwang JS, Kang ES, Ham SA, Yoo T, Lee H, Paek KS, Park C, Kim JH, Lim DS, Seo HG - Mediators Inflamm. (2012)

Rosiglitazone inhibits Poly (I:C)-induced HMGB1 release in RAW 264.7 cells. (a) Cells grown to 60% confluency were incubated with serum-free medium for 24 h and then stimulated with LPS and/or Poly (I:C) in the presence or absence of rosiglitazone for 24 h. Equal volumes of conditioned media were subjected to Western blot analysis for the detection of HMGB1. Ponceau S staining was used as a loading control. (b) At the same time, total protein was extracted, fractioned by electrophoresis, and immunoblotted with the indicated antibodies. The results shown are representative of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539392&req=5

fig2: Rosiglitazone inhibits Poly (I:C)-induced HMGB1 release in RAW 264.7 cells. (a) Cells grown to 60% confluency were incubated with serum-free medium for 24 h and then stimulated with LPS and/or Poly (I:C) in the presence or absence of rosiglitazone for 24 h. Equal volumes of conditioned media were subjected to Western blot analysis for the detection of HMGB1. Ponceau S staining was used as a loading control. (b) At the same time, total protein was extracted, fractioned by electrophoresis, and immunoblotted with the indicated antibodies. The results shown are representative of three independent experiments.
Mentions: To examine whether rosiglitazone has a specific effect against LPS stimulation in the inhibition of HMGB1 release, RAW 264.7 cells were stimulated with Poly (I:C), a well-known ligand of Toll-like receptor (TLR) 3, in the presence or absence of rosiglitazone for 24 h. Rosiglitazone significantly inhibited Poly (I:C)-induced HMGB1 release, but not affect expression levels of HMGB1 (Figure 2), indicating that effect of rosiglitazone on the inhibition of HMGB1 release is not limited to the LPS.

Bottom Line: Among the ligands of PPAR, the effect of rosiglitazone, a specific ligand for PPARγ, was superior in the inhibition of HMGB1 release induced by LPS.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.

ABSTRACT
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 PPARγ, 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 PPARγ with small interfering RNA or GW9662-mediated inhibition of PPARγ abolished the effect of rosiglitazone on HMGB1 release. Furthermore, the overexpression of PPARγ 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.

Show MeSH
Related in: MedlinePlus