Expression of retinoid receptors during human monocyte differentiation in vitro

1 alpha,25-Dihydroxyvitamin D-3 (1,25(OH)(2)VD3) and retinoic acid (RA) mod ulate the activation of monocytes (MO) and their differentiation into macro phages (MAC). As these effects are mostly mediated by heterodimers or homod imers of the specific nuclear receptors for 1,25(OH)(2)VD3 and RA, we inves tigated the expression of the retinoic acid receptors (RAR) alpha, beta, an d gamma and the retinoid X-receptor (RXR) a in MO during differentiation in to MAC or dendritic cells (DC). The mRNA of all investigated receptors exce pt RAR beta 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 o f RAR gamma declined, whereas RAR alpha and RXR alpha were constantly expre ssed at a high level. Despite the strong expression of RAR alpha and RXR al pha 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 exp ression of these receptors at protein level. This suggests that a posttrans criptional or posttranslational mechanism of receptor regulation is occurri ng in these cells, and in particular in the DC. The inverse regulation of R A receptor expression and protein levels between MAC and DC may control the responsiveness of these cells to 1,25(OH)(2)VD3 and RA. (C) 2000 Academic Press.