PPARgamma is not a critical mediator of primary monocyte differentiation or foam cell formation

Autor: Stephen A. Smith, Colin H. Macphee, Lisa Patel, Phil Coxon, Ian C B Marshall, John C. Clapham, Steven J. Charlton, Kitty Moores, Suzanna J. Newman, Gary B.T. Moore
Rok vydání: 2002
Předmět:
CD36 Antigens
Light
Receptors
Retinoic Acid
CD36
Receptors
Cytoplasmic and Nuclear
Ligands
Biochemistry
Monocytes
Scattering
Radiation
Cells
Cultured
Foam cell
Liver X Receptors
biology
Cell Differentiation
Flow Cytometry
Orphan Nuclear Receptors
Cell biology
DNA-Binding Proteins
Lipoproteins
LDL
medicine.anatomical_structure
Matrix Metalloproteinase 9
Monocyte differentiation
lipids (amino acids
peptides
and proteins)
Rosiglitazone
medicine.drug
ATP Binding Cassette Transporter 1
Tetrahydronaphthalenes
Biophysics
Downregulation and upregulation
medicine
Humans
RNA
Messenger
Molecular Biology
Dose-Response Relationship
Drug
Activator (genetics)
Interleukin-6
Monocyte
Macrophages
Nicotinic Acids
Cell Biology
Oligonucleotides
Antisense
Thiazoles
Retinoid X Receptors
ABCA1
biology.protein
ATP-Binding Cassette Transporters
Thiazolidinediones
Foam Cells
Transcription Factors
Zdroj: Biochemical and biophysical research communications. 290(2)
ISSN: 0006-291X
Popis: In the present report we clarify the role of PPARgamma in differentiation and function of human-derived monocyte/macrophages in vitro. Rosiglitazone, a selective PPARgamma activator, had no effect on the kinetics of appearance of monocyte/macrophage differentiation markers or on cell size or granularity. Depletion of PPARgamma by more than 90% using antisense oligonucleotides did not influence accumulation of oxidized LDL or prevent the upregulation of CD36 that normally accompanies oxLDL treatment. In contrast, PPARgamma depletion reduced the expression of ABCA1 and LXRalpha mRNAs. Metalloproteinase-9 expression, a marker of atherosclerotic plaque vulnerability, was suppressed by rosiglitazone. We conclude that activation of PPARgamma does not affect monocyte/macrophage differentiation. In addition, PPARgamma is not absolutely required for oxLDL-driven lipid accumulation, but is required for full expression of ABCA1 and LXRalpha. Our data support a role for rosiglitazone as a potential directly acting antiatherosclerotic agent.
Databáze: OpenAIRE
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