Expression of retinoid receptors during human monocyte differentiation in vitro

Abstract

1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)VD(3)) and retinoic acid (RA) modulate the activation of monocytes (MO) and their differentiation into macrophages (MAC). As these effects are mostly mediated by heterodimers or homodimers of the specific nuclear receptors for 1,25(OH)(2)VD(3) and RA, we investigated the expression of the retinoic acid receptors (RAR) alpha, beta, and gamma and the retinoid X-receptor (RXR) alpha in MO during differentiation into MAC or dendritic cells (DC). The mRNA of all investigated receptors except RARbeta was detected in short-term cultured MO. During differentiation of MO to MAC the mRNA expression of the RA receptors decreased. In contrast, along the differentiation pathway of MO to DC, only the mRNA expression of RARgamma declined, whereas RARalpha and RXRalpha were constantly expressed at a high level. Despite the strong expression of RARalpha and RXRalpha at mRNA level in MO-derived DC, the protein expression of the receptors was low in these cells. However, MO and MO-derived MAC showed a strong expression of these receptors at protein level. This suggests that a posttranscriptional or posttranslational mechanism of receptor regulation is occurring in these cells, and in particular in the DC. The inverse regulation of RA receptor expression and protein levels between MAC and DC may control the responsiveness of these cells to 1,25(OH)(2)VD(3) and RA.