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

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) induce...

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Main Authors:	Hwang, Jung Seok, Kang, Eun Sil, Ham, Sun Ah, Yoo, Taesik, Lee, Hanna, Paek, Kyung Shin, Park, Chankyu, Kim, Jin-Hoi, Lim, Dae-Seog, Seo, Han Geuk
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539392/

id	pubmed-3539392
recordtype	oai_dc
spelling	pubmed-35393922013-01-11 Activation of Peroxisome Proliferator-Activated Receptor γ by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1 Hwang, Jung Seok Kang, Eun Sil Ham, Sun Ah Yoo, Taesik Lee, Hanna Paek, Kyung Shin Park, Chankyu Kim, Jin-Hoi Lim, Dae-Seog Seo, Han Geuk Research Article 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. Hindawi Publishing Corporation 2012 2012-12-20 /pmc/articles/PMC3539392/ /pubmed/23316104 http://dx.doi.org/10.1155/2012/352807 Text en Copyright © 2012 Jung Seok Hwang et al. https://creativecommons.org/licenses/by/3.0/ 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hwang, Jung Seok Kang, Eun Sil Ham, Sun Ah Yoo, Taesik Lee, Hanna Paek, Kyung Shin Park, Chankyu Kim, Jin-Hoi Lim, Dae-Seog Seo, Han Geuk
spellingShingle	Hwang, Jung Seok Kang, Eun Sil Ham, Sun Ah Yoo, Taesik Lee, Hanna Paek, Kyung Shin Park, Chankyu Kim, Jin-Hoi Lim, Dae-Seog Seo, Han Geuk Activation of Peroxisome Proliferator-Activated Receptor γ by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1
author_facet	Hwang, Jung Seok Kang, Eun Sil Ham, Sun Ah Yoo, Taesik Lee, Hanna Paek, Kyung Shin Park, Chankyu Kim, Jin-Hoi Lim, Dae-Seog Seo, Han Geuk
author_sort	Hwang, Jung Seok
title	Activation of Peroxisome Proliferator-Activated Receptor γ by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1
title_short	Activation of Peroxisome Proliferator-Activated Receptor γ by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1
title_full	Activation of Peroxisome Proliferator-Activated Receptor γ by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1
title_fullStr	Activation of Peroxisome Proliferator-Activated Receptor γ by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1
title_full_unstemmed	Activation of Peroxisome Proliferator-Activated Receptor γ by Rosiglitazone Inhibits Lipopolysaccharide-Induced Release of High Mobility Group Box 1
title_sort	activation of peroxisome proliferator-activated receptor γ by rosiglitazone inhibits lipopolysaccharide-induced release of high mobility group box 1
description	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.
publisher	Hindawi Publishing Corporation
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539392/
_version_	1611945166644445184

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

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