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

被引:447
作者
Moore, KJ
Rosen, ED
Fitzgerald, ML
Randow, F
Andersson, LP
Altshuler, D
Milstone, DS
Mortensen, RM
Spiegelman, BM
Freeman, MW [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Med, Lipid Metab Unit, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA
[4] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[5] MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA
[6] Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA
[7] Univ Michigan, Dept Physiol, Div Endocrine, Ann Arbor, MI 48109 USA
关键词
D O I
10.1038/83328
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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收藏
页码:41 / 47
页数:7
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