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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| _version_ | 1832566617897172992 |
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| author | Yu-Jui Yvonne Wan Mostafa Z. Badr |
| author_facet | Yu-Jui Yvonne Wan Mostafa Z. Badr |
| author_sort | Yu-Jui Yvonne Wan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-67cfebf8ce60488cb97378124b5e71ec |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2006-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-67cfebf8ce60488cb97378124b5e71ec2025-02-03T01:03:36ZengWileyPPAR Research1687-47571687-47652006-01-01200610.1155/PPAR/2006/9634196341Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor AlphaYu-Jui Yvonne Wan0Mostafa Z. Badr1Department of Pharmacology, Toxicology & Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, USADivision of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USAIt 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.http://dx.doi.org/10.1155/PPAR/2006/96341 |
| spellingShingle | Yu-Jui Yvonne Wan Mostafa Z. Badr Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor Alpha PPAR Research |
| title | Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR
Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor
Alpha |
| title_full | Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR
Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor
Alpha |
| title_fullStr | Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR
Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor
Alpha |
| title_full_unstemmed | Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR
Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor
Alpha |
| title_short | Inhibition of Carrageenan-Induced Cutaneous Inflammation by PPAR
Agonists Is Dependent on Hepatocyte-Specific Retinoid X Receptor
Alpha |
| title_sort | inhibition of carrageenan induced cutaneous inflammation by ppar agonists is dependent on hepatocyte specific retinoid x receptor alpha |
| url | http://dx.doi.org/10.1155/PPAR/2006/96341 |
| work_keys_str_mv | AT yujuiyvonnewan inhibitionofcarrageenaninducedcutaneousinflammationbypparagonistsisdependentonhepatocytespecificretinoidxreceptoralpha AT mostafazbadr inhibitionofcarrageenaninducedcutaneousinflammationbypparagonistsisdependentonhepatocytespecificretinoidxreceptoralpha |