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

Attila Szanto, Laszlo Nagy

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1935-1943
Number of pages9
JournalMolecular Pharmacology
Volume67
Issue number6
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

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Peroxisome Proliferator-Activated Receptors
Retinoids
Myeloid Cells
Lipids
Gene Expression
Macrophages
Cytoplasmic and Nuclear Receptors
Monocytes
Scavenger Receptors
Retinoic Acid Receptors
Lipid Metabolism
Cell Differentiation
Transcription Factors

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Retinoids potentiate peroxisome proliferator-activated receptor γ action in differentiation, gene expression, and lipid metabolic processes in developing myeloid cells",
abstract = "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.",
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AU - Nagy, Laszlo

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N2 - 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.

AB - 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.

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