Retinoids potentiate peroxisome proliferator-activated receptor γ action in differentiation, gene expression, and lipid metabolic processes in developing myeloid cells

Nuclear hormone receptors have been shown to be important transcription factors for regulating lipid metabolism in myeloid cells and were also implicated in differentiation processes of the myeloid lineage and macrophages. Peroxisome proliferator-activated receptor γ(PPARγ) seems to be a key component of lipid uptake by inducing the scavenger receptor CD36 that mediates oxidized low-density lipoprotein uptake in macrophages. Retinoic acid receptors, on the other hand, were also shown to play important roles in myeloid cell differentiation. In this study, we present evidence for a cross-talk between these two nuclear receptor pathways in myeloid cells. We show that expression level of PPARγ increases with the degree of monocyte/macrophage commitment during maturation. Activation of PPARγ leads to the increased expression of maturation markers (e.g., CD14, CD36). It is interesting that retinoid treatment potentiates PPARγ's ability to induce transcription of its target genes. Retinoid-increased PPARγ response is sufficient for enhancing lipid uptake. Our data, taken together, indicate that the expression level of PPARγ increases during monocyte/macrophage development. PPARγ activity can be enhanced by retinoids at least in part via increasing PPARγ expression level. These observations can be exploited to enhance therapeutically beneficial PPAR responses in myeloid cells.