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

Nat Med. 2001 Jan;7(1):41-7. doi: 10.1038/83328.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • CD36 Antigens / immunology
  • Cell Differentiation / physiology*
  • Cholesterol / metabolism*
  • DNA Probes
  • Hypoglycemic Agents / pharmacology
  • Lipoproteins, LDL / metabolism
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Thiazoles / pharmacology
  • Transcription Factors / physiology*


  • CD36 Antigens
  • DNA Probes
  • Hypoglycemic Agents
  • Lipoproteins, LDL
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Transcription Factors
  • oxidized low density lipoprotein
  • Cholesterol