Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor Alpha
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 antiede...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2006-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/PPAR/2006/96341 |
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| Summary: | 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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| ISSN: | 1687-4757 1687-4765 |