Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPAR(gamma):RXR heterodimers: comparison with other polyunsaturated fatty acids.
There is accumulating evidence that omega-3 fatty acids may modulate immune responses. When monocytes were differentiated to dendritic cells (DCs) in the presence of docosahexaenoic acid (DHA), the expression of costimulatory and antigen presentation markers was altered in a concentration-dependent way, positively or negatively, depending on the markers tested and the maturation stage of the DCs. Changes induced by eicosapentaenoic acid and linoleic acid were similar but less intense than those of DHA, whereas oleic acid had almost no effect. DHA-treated, mature DCs showed inhibition of IL-6 expression and IL-10 and IL-12 secretion, and their lymphoproliferative stimulation capacity was impaired. The phenotypic alterations of DCs induced by DHA were similar to those already reported for Rosiglitazone (Rosi), a peroxisome proliferator-activated receptor gamma (PPAR gamma) activator, and the retinoid 9-cis-retinoic acid (9cRA), a retinoid X receptor (RXR) activator. Moreover, DHA induced the expression of PPAR gamma target genes pyruvate dehydrogenase kinase-4 and aP-2 in immature DCs. The combination of DHA with Rosi or 9cRA produced additive effects. Furthermore, when DCs were cultured in the presence of a specific PPAR gamma inhibitor, all of the changes induced by DHA were blocked. Together, these results strongly suggest that the PPAR gamma:RXR heterodimer is the pathway component activated by DHA to induce its immunomodulatory effect on DCs.
Zapata-Gonzalez
Fernando
F
Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain.
Rueda
Felix
F
Petriz
Jordi
J
Domingo
Pere
P
Villarroya
Francesc
F
Diaz-Delfin
Julieta
J
de Madariaga
Maria A
MA
Domingo
Joan C
JC
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D019281:Dimerization; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000166:cytology; D047495:PPAR gamma / Q000494:pharmacology*; D047488:Retinoid X Receptors / Q000494:pharmacology*
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D047495:PPAR gamma; D047488:Retinoid X Receptors; D004281:Docosahexaenoic Acids