|
|
Blood, 1 November 2007, Vol. 110, No. 9, pp. 3271-3280.
Prepublished online as a Blood First Edition Paper on July 30, 2007; DOI 10.1182/blood-2007-06-096222.
 Previous Article | Next Article 
Submitted June 15, 2007
Accepted July 25, 2007
PPAR regulates the function of human dendritic cells primarily by altering lipid metabolism
Istvan Szatmari, Daniel Torocsik, Maura Agostini, Tibor Nagy, Mark Gurnell, Endre Barta, Krishna Chatterjee, and Laszlo Nagy*
Department of Biochemostry & Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary
Department of Medicine, University of Cambridge, Cambridge, United Kingdom
Department of Bioinformatics, Agricultural Biotechnology Center, Godollo, Hungary
* Corresponding author; email: lnagy{at}indi.biochem.dote.hu.
Activation of the lipid-regulated nuclear receptor, Peroxisome Proliferator-Activated Receptor gamma (PPAR ) modifies the immunophenotype of monocyte-derived dendritic cells (DCs). However it has not been analyzed in a systematic manner how lipid metabolism and immune regulation are connected at the transcriptional level via this receptor. Here we present the genome-wide expression analyses of PPAR-instructed human DCs. Receptor activation was achieved by exogenous, synthetic as well as endogenous, natural means. Over 1000 transcripts are regulated during DC development by activation of PPAR, half of the changes are positive effects. These changes appear to enhance and modulate the robust gene expression alterations associated with monocyte to DC transition. Strikingly, only genes related to lipid metabolism are over-represented among early-induced genes. As a net consequence lipid accumulation appears to be diminished in these cells. In contrast, genes related to immune response are regulated after 24 hours implying the existence of indirect mechanisms of modulation. Receptor-dependence was established by using DCs of patients harboring a dominant negative mutation of PPAR. Our data show that PPAR acts as a mostly positive transcriptional regulator in human developing DCs acting primarily through controlling genes involved in lipid metabolism and via this, indirectly modifying the immune phenotype.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Linking metabolism to immunity through PPAR
- Chaitra Marathe and Peter Tontonoz
Blood 2007 110: 3092-3093.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
A. Are, L. Aronsson, S. Wang, G. Greicius, Y. K. Lee, J.-A. Gustafsson, S. Pettersson, and V. Arulampalam
Enterococcus faecalis from newborn babies regulate endogenous PPAR{gamma} activity and IL-10 levels in colonic epithelial cells
PNAS,
February 12, 2008;
105(6):
1943 - 1948.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
