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Fenofibrate Enhances the In Vitro Differentiation of Foxp3+ Regulatory T Cells in Mice.
- Source :
-
PPAR Research . 2012, Special section p1-10. 10p. 6 Graphs. - Publication Year :
- 2012
-
Abstract
- Foxp3+ regulatory T cells (Tregs) play a critical role in maintaining immune self-tolerance. Reduced number and activity of Tregs are usually found in autoimmune and inflammatory diseases, and enhancing the differentiation of Tregs may be a promising therapeutic strategy. Some reports suggested an anti-inflammatory and anti-autoimmune potential for fenofibrate, a hypolipidemic drug used worldwide, whose lipid effects are mediated by the activation of peroxisome proliferator-activated receptor α (PPARα). In the present paper, we found that fenofibrate dose-dependently increased transforming growth factor-β and interleukin-2-induced Treg differentiation in vitro, by 1.96-fold from 0 to 20 μM(12.59±1.34% to 24.69±3.03%,P < 0.05). Other PPARα activators, WY14643 (100 μM), gemfibrozil (50μM), and bezafibrate (30 μM), could not enhance Treg differentiation. In addition, PPARα could not upregulate the promoter activity of the Treg-specific transcription factor Foxp3. Fenofibrate might exert its function by enhancing Smad3 phosphorylation, a critical signal in Treg differentiation, via Akt suppression. Our work reveals a new PPARα independent anti-inflammatory mechanism of fenofibrate in up-regulating mouse Treg differentiation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16874757
- Database :
- Academic Search Index
- Journal :
- PPAR Research
- Publication Type :
- Academic Journal
- Accession number :
- 84956457
- Full Text :
- https://doi.org/10.1155/2012/529035