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. copyright © 2011 atsuki yamamoto et al.