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Human dendritic cell activities are modulated by the omega‐3 fatty acid, docosahexaenoic acid, mainly through PPARγ:RXR heterodimers: comparison with other polyunsaturated fatty acids
Author(s) -
ZapataGonzalez Fernando,
Rueda Felix,
Petriz Jordi,
Domingo Pere,
Villarroya Francesc,
DiazDelfin Julieta,
de Madariaga Maria A.,
Domingo Joan C.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1007688
Subject(s) - docosahexaenoic acid , retinoid x receptor , biology , peroxisome proliferator activated receptor , retinoic acid , eicosapentaenoic acid , polyunsaturated fatty acid , retinoid , retinoid x receptor alpha , biochemistry , endocrinology , receptor , fatty acid , medicine , nuclear receptor , transcription factor , gene
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 γ (PPARγ) activator, and the retinoid 9‐cis‐retinoic acid (9cRA), a retinoid X receptor (RXR) activator. Moreover, DHA induced the expression of PPARγ 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 PPARγ inhibitor, all of the changes induced by DHA were blocked. Together, these results strongly suggest that the PPARγ:RXR heterodimer is the pathway component activated by DHA to induce its immunomodulatory effect on DCs.