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

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.