The role of PPAR-gamma in macrophage differentiation and cholesterol uptake.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), the transcription factor target of the anti-diabetic thiazolidinedione (TZD) drugs, is reported to mediate macrophage differentiation and inflammatory responses. Using PPAR-gamma-deficient stem cells, we demonstrate that PPAR-gamma is neither essential for myeloid development, nor for such mature macrophage functions as phagocytosis and inflammatory cytokine production. PPAR-gamma is required for basal expression of CD36, but not for expression of the other major scavenger receptor responsible for uptake of modified lipoproteins, SR-A. In wild-type macrophages, TZD treatment divergently regulated CD36 and class A macrophage-scavenger receptor expression and failed to induce significant cellular cholesterol accumulation, indicating that TZDs may not exacerbate macrophage foam-cell formation.
Moore
K J
KJ
Lipid Metabolism Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Rosen
E D
ED
Fitzgerald
M L
ML
Randow
F
F
Andersson
L P
LP
Altshuler
D
D
Milstone
D S
DS
Mortensen
R M
RM
Spiegelman
B M
BM
Freeman
M W
MW
D000818:Animals; D001483:Base Sequence; D018955:CD36 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism*; D015342:DNA Probes; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*
D018955:CD36 Antigens; D015342:DNA Probes; D007004:Hypoglycemic Agents; D008077:Lipoproteins, LDL; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D014157:Transcription Factors; C099252:oxidized low density lipoprotein; D002784:Cholesterol