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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

Administration of rosiglitazone post-LPS treatment also attenuates LPS-induced release of HMGB1 in RAW 264.7 cells. Cells were grown to 60% confluency, incubated with serum-free medium for 24 h, and then treated with LPS. Rosiglitazone was administered at the indicated time points post-LPS treatment for 24 h. Conditioned medium was subjected to Western blot analysis for the determination of HMGB1 levels. Ponceau S staining was used as a loading control. The results shown are representative of three independent experiments.
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fig3: Administration of rosiglitazone post-LPS treatment also attenuates LPS-induced release of HMGB1 in RAW 264.7 cells. Cells were grown to 60% confluency, incubated with serum-free medium for 24 h, and then treated with LPS. Rosiglitazone was administered at the indicated time points post-LPS treatment for 24 h. Conditioned medium was subjected to Western blot analysis for the determination of HMGB1 levels. Ponceau S staining was used as a loading control. The results shown are representative of three independent experiments.

Mentions: Because administering rosiglitazone to cells prior to treatment with LPS was effective in the inhibition of LPS-induced release of HMGB1, the effect of rosiglitazone when supplied at time points following LPS treatment was examined. When cells were treated with LPS, an increase in the level of released HMGB1 was detected at 24 h, and this increase was markedly reduced by supplying rosiglitazone to cells following LPS treatment. This effect was observed in cells when rosiglitazone was administered up to 6 h after LPS treatment and also, to a lesser extent, in cells receiving rosiglitazone up to 18 h after LPS treatment (Figure 3), suggesting that rosiglitazone could be useful in treatment, as well as in the prevention of HMGB1 release.


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)

Administration of rosiglitazone post-LPS treatment also attenuates LPS-induced release of HMGB1 in RAW 264.7 cells. Cells were grown to 60% confluency, incubated with serum-free medium for 24 h, and then treated with LPS. Rosiglitazone was administered at the indicated time points post-LPS treatment for 24 h. Conditioned medium was subjected to Western blot analysis for the determination of HMGB1 levels. Ponceau S staining was used as a loading control. 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

fig3: Administration of rosiglitazone post-LPS treatment also attenuates LPS-induced release of HMGB1 in RAW 264.7 cells. Cells were grown to 60% confluency, incubated with serum-free medium for 24 h, and then treated with LPS. Rosiglitazone was administered at the indicated time points post-LPS treatment for 24 h. Conditioned medium was subjected to Western blot analysis for the determination of HMGB1 levels. Ponceau S staining was used as a loading control. The results shown are representative of three independent experiments.
Mentions: Because administering rosiglitazone to cells prior to treatment with LPS was effective in the inhibition of LPS-induced release of HMGB1, the effect of rosiglitazone when supplied at time points following LPS treatment was examined. When cells were treated with LPS, an increase in the level of released HMGB1 was detected at 24 h, and this increase was markedly reduced by supplying rosiglitazone to cells following LPS treatment. This effect was observed in cells when rosiglitazone was administered up to 6 h after LPS treatment and also, to a lesser extent, in cells receiving rosiglitazone up to 18 h after LPS treatment (Figure 3), suggesting that rosiglitazone could be useful in treatment, as well as in the prevention of HMGB1 release.

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