Involvement of the retinoid X receptor ligand in the anti-inflammatory effect induced by peroxisome proliferator-activated receptor agonist in vivo

Atsuki Yamamoto, Hiroki Kakuta, Hiroyuki Miyachi, Yukio Sugimoto

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9 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor γ(PPAR) forms a heterodimeric DNA-binding complex with retinoid X receptors (RXRs). It has been reported that the effect of the PPAR agonist is reduced in hepatocyte RXR-deficient mice. Therefore, it is suggested that the endogenous RXR ligand is involved in the PPAR agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPAR-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPAR agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPARγ antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPAR agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPARγ antagonist. PPAR agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPAR agonist-induced anti-inflammatory effect.

Original languageEnglish
Article number840194
JournalPPAR Research
DOIs
Publication statusPublished - 2011

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Retinoid X Receptors
Peroxisome Proliferator-Activated Receptors
Anti-Inflammatory Agents
Ligands
pioglitazone
Carrageenan
Hepatocytes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Drug Discovery

Cite this

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title = "Involvement of the retinoid X receptor ligand in the anti-inflammatory effect induced by peroxisome proliferator-activated receptor agonist in vivo",
abstract = "Peroxisome proliferator-activated receptor γ(PPAR) forms a heterodimeric DNA-binding complex with retinoid X receptors (RXRs). It has been reported that the effect of the PPAR agonist is reduced in hepatocyte RXR-deficient mice. Therefore, it is suggested that the endogenous RXR ligand is involved in the PPAR agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPAR-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPAR agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPARγ antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPAR agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPARγ antagonist. PPAR agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPAR agonist-induced anti-inflammatory effect.",
author = "Atsuki Yamamoto and Hiroki Kakuta and Hiroyuki Miyachi and Yukio Sugimoto",
year = "2011",
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language = "English",
journal = "PPAR Research",
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AU - Yamamoto, Atsuki

AU - Kakuta, Hiroki

AU - Miyachi, Hiroyuki

AU - Sugimoto, Yukio

PY - 2011

Y1 - 2011

N2 - Peroxisome proliferator-activated receptor γ(PPAR) forms a heterodimeric DNA-binding complex with retinoid X receptors (RXRs). It has been reported that the effect of the PPAR agonist is reduced in hepatocyte RXR-deficient mice. Therefore, it is suggested that the endogenous RXR ligand is involved in the PPAR agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPAR-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPAR agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPARγ antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPAR agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPARγ antagonist. PPAR agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPAR agonist-induced anti-inflammatory effect.

AB - Peroxisome proliferator-activated receptor γ(PPAR) forms a heterodimeric DNA-binding complex with retinoid X receptors (RXRs). It has been reported that the effect of the PPAR agonist is reduced in hepatocyte RXR-deficient mice. Therefore, it is suggested that the endogenous RXR ligand is involved in the PPAR agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPAR-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPAR agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPARγ antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPAR agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPARγ antagonist. PPAR agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPAR agonist-induced anti-inflammatory effect.

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