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Published on: March 28, 2013
The role of PPAR-gamma in macrophage differentiation and cholesterol uptake
K J Moore1, E D Rosen, M L Fitzgerald
1Lipid Metabolism Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
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.
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