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

KJ Moore, ED Rosen, ML Fitzgerald, F Randow… - Nature medicine, 2001 - nature.com
KJ Moore, ED Rosen, ML Fitzgerald, F Randow, LP Andersson, D Altshuler, DS Milstone…
Nature medicine, 2001nature.com
Peroxisome proliferator-activated receptor-γ (PPAR-γ), the transcription factor target of the
anti-diabetic thiazolidinedione (TZD) drugs, is reported to mediate macrophage
differentiation and inflammatory responses. Using PPAR-γ–deficient stem cells, we
demonstrate that PPAR-γ is neither essential for myeloid development, nor for such mature
macrophage functions as phagocytosis and inflammatory cytokine production. PPAR-γ is
required for basal expression of CD36, but not for expression of the other major scavenger …
Abstract
Peroxisome proliferator-activated receptor-γ (PPAR-γ), the transcription factor target of the anti-diabetic thiazolidinedione (TZD) drugs, is reported to mediate macrophage differentiation and inflammatory responses. Using PPAR-γ–deficient stem cells, we demonstrate that PPAR-γ is neither essential for myeloid development, nor for such mature macrophage functions as phagocytosis and inflammatory cytokine production. PPAR-γ 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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