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 (PPARγ) 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 PPARγ agonist-induced anti-inflammatory effect. However, the participation of the RXR ligand in the PPARγ-induced anti-inflammatory effect is unknown. Here, we investigated the influence of RXR antagonist on the anti-inflammatory effect of PPARγ agonist pioglitazone in carrageenan test. In addition, we also examined the influence of PPAR antagonist on the anti-inflammatory effect induced by RXR agonist NEt-3IP. The RXR antagonist suppressed the antiedema effect of PPARγ agonist. In addition, the anti-inflammatory effect of RXR agonist was suppressed by PPARγ antagonist. PPARγ agonist-induced anti-inflammatory effects were reversed by the RXR antagonist. Thus, we showed that the endogenous RXR ligand might contribute to the PPARγ agonist-induced anti-inflammatory effect.

Optimization, Biopharmaceutical Profile and Therapeutic Efficacy of Pioglitazone-loaded PLGA-PEG Nanospheres as a Novel Strategy for Ocular Inflammatory Disorders

“…However, it has been described that an ophthalmic solution containing 0.1% PGZ inhibited inflammation, decreased the fibrotic reaction, and prevented corneal neovascularization in the cornea from the early phase after alkali burn injury in rats (4). However, in another study, it was shown that the PGZ inhibited intraocular concentrations of TNF-α and IL-6 in the endogenous uveitis model (2). These results demonstrated that PPARγ agonists may represent a way of moving forward with a treatment strategy focused on clinical applications in inflammatory processes and better wound healing.…”

“…antifibrotic, anti-tumor effects, and neuroprotection. Moreover , it has a protective effect on inflammatory ocular process (1)(2)(3)(4).…”

“…The assay was carried out using Franz diffusion cells and the tissue was fixed between the donor and receptor compartment. The area in which the permeation could work was 0.64 cm2 . The receptor compartment was filled with a freshly prepared transcutol/water solution (60/40 v/v) and kept at 32.0 ± 0.5 ºC and stirred continuously for 6 hours.…”

Gene Expression of Peroxisome Proliferator-Activated Receptor Is Upregulated by Nonsteroidal Anti-Inflammatory Drugs and Correlates with Cyclooxygenase-2 Suppression In Inflamed-Rat Muscle

“…A significant negative correlation was found between PPARγ1 and edema. The expression levels of both PPAR and RXR mRNA have been found to be decreased in animal model with liver inflammation, indicating that PPARγ and RXR agonists may play an important role in response to inflammation and fibrosis (28).…”

PPARγ agonist-loaded PLGA-PEG nanocarriers as a potential treatment for Alzheimer’s disease: in vitro and in vivo studies

“…The PPARγ receptors have various functions including anti-angiogenic, antifibrotic, anti-inflammatory and anti-tumor effects. [7][8][9][10] PGZ is also neuroprotective in models of neurodegenerative disorders, 10 highlighting PPARγ agonists as a promising treatment for AD. 11 Thus, PGZ has been reported to reduce oxidative stress, normalize cerebral blood flow and glucose uptake, increase neuronal activity and exert positive effects on cerebrovascular functions in an animal model of AD.…”