The role of PPAR-gamma in macrophage differentiation and cholesterol uptake

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), the transcri ption 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 n either essential for myeloid development, nor for such mature macrophage fu nctions 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 an d class A macrophage-scavenger receptor expression and failed to induce sig nificant cellular cholesterol accumulation, indicating that TZDs may not ex acerbate macrophage foam-cell formation.