Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR
Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor
<i>Alpha</i>

Wan, Yu-Jui Yvonne; Badr, Mostafa Z.

doi:https://doi.org/10.1155/PPAR/2006/96341

PPAR Research

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Research Article | Open Access

Volume 2006 | Article ID 096341 | https://doi.org/10.1155/PPAR/2006/96341

Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor Alpha

Yu-Jui Yvonne Wan¹and Mostafa Z. Badr²

Received30 Jan 2006

Revised20 Apr 2006

Accepted21 Apr 2006

Published04 Jul 2006

Abstract

It has been proposed that PPAR-dependent, accelerated catabolism of proinflammatory mediators may contribute to the fast resolution of inflammation. Because retinoid X receptors are obligate heterodimer partners of PPARs, we investigated the impact of deleting hepatocyte-specific RXRα on the antiedema effect of PPAR agonists. In wild-type mice (WT), pretreatment with the PPARα agonist perfluorooctanoic acid diminished carrageenan-induced paw edema by 66±10%. This effect was essentially absent (13±8%) in hepatocyte-specific RXRα-deficient mice. Similarly, pretreatment of WT mice with the PPARδ agonist L-783483 or the PPARγ agonist L-805645 caused 54±1% and 38±8% reduction in carrageenan-induced paw edema, respectively. These effects were also significantly diminished or absent in hepatocyte-specific RXRα-deficient mice. In contrast, aspirin reduced carrageenan-induced paw edema equally in WT and hepatocyte-specific RXRα-deficient mice. The identification of RXRα as an important factor involved in the antiedema effect produced by agonists of the three PPAR subtypes is a significant achievement towards the goal of designing novel, effective anti-inflammatory drugs.

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Copyright

Copyright © 2006 Yu-Jui Yvonne Wan and Mostafa Z. Badr. 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.

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