TY - JOUR
T1 - 9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) ligand, exerts immunosuppressive effects on dendritic cells by RXR-dependent activation: Inhibition of peroxisome proliferator-activated receptor γ blocks some of the 9cRA activities, and precludes them to mature phenotype development
AU - Zapata-Gonzalez, Fernando
AU - Rueda, Félix
AU - Petriz, Jordi
AU - Domingo, Pere
AU - Villarroya, Francesc
AU - De Madariaga, Africa
AU - Domingo, Joan C.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - At nanomolar range, 9-cis-retinoic acid (9cRA) was able to interfere in the normal differentiation process from human monocyte to immature dendritic cell (DC) and produced a switch in mature DCs to a less stimulatory mode than untreated cells. 9cRA-treated mature DCs secreted high levels of IL-10 with an IL-12 reduced production. The phenotypic alterations unleashed by 9cRA were similar but not identical to other specific retinoid X receptor (RXR) agonists and to those already reported for rosiglitazone, a PPARγ activator, on DCs. The simultaneous addition of 9cRA and rosiglitazone on DCs displayed additive effects. Moreover, addition to cultures of G W9662, a specific inhibitor of PPARγ, or the RXR pan-antagonist HX603, blocked these changes. All these results suggest an activation of PPARγ-RXR and other RXR containing dimers by 9cRA in DCs. Finally, both GW9662 and HX603 by themselves altered the maturation process unleashed by TNFα, poly(I:C) or LPS on human DCs further suggesting that the heterodimer PPARγ-RXR must fulfill a significant role in the physiological maturation process of these cells in addition to the repressing effects reported till now for this nuclear receptor. Copyright © 2007 by The American Association of Immunologists, Inc.
AB - At nanomolar range, 9-cis-retinoic acid (9cRA) was able to interfere in the normal differentiation process from human monocyte to immature dendritic cell (DC) and produced a switch in mature DCs to a less stimulatory mode than untreated cells. 9cRA-treated mature DCs secreted high levels of IL-10 with an IL-12 reduced production. The phenotypic alterations unleashed by 9cRA were similar but not identical to other specific retinoid X receptor (RXR) agonists and to those already reported for rosiglitazone, a PPARγ activator, on DCs. The simultaneous addition of 9cRA and rosiglitazone on DCs displayed additive effects. Moreover, addition to cultures of G W9662, a specific inhibitor of PPARγ, or the RXR pan-antagonist HX603, blocked these changes. All these results suggest an activation of PPARγ-RXR and other RXR containing dimers by 9cRA in DCs. Finally, both GW9662 and HX603 by themselves altered the maturation process unleashed by TNFα, poly(I:C) or LPS on human DCs further suggesting that the heterodimer PPARγ-RXR must fulfill a significant role in the physiological maturation process of these cells in addition to the repressing effects reported till now for this nuclear receptor. Copyright © 2007 by The American Association of Immunologists, Inc.
M3 - Article
VL - 178
SP - 6130
EP - 6139
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -